Preadolescents and Their Mothers as Oral Health-Promoting Actors : Non-biologic Determinants of Oral Health among Turkish and Finnish Preadolescents

Is oral health becoming a part of the global health culture? Oral health seems to turn out to be part of the global health culture, according to the findings of a thesis-research, Institute of Dentistry, University of Helsinki. The thesis is entitled as “Preadolescents and Their Mothers as Oral Health-Promoting Actors: Non-biologic Determinants of Oral Health among Turkish and Finnish Preadolescents.” The research was supervised by Prof.Murtomaa and led by Dr.A.Basak Cinar. It was conducted as a cross-sectional study of 611 Turkish and 223 Finnish school preadolescents in Istanbul and Helsinki, from the fourth, fifth, and sixth grades, aged 10 to 12, based on self-administered and pre-tested health behavior questionnaires for them and their mothers as well as the youth’s oral health records. Clinically assessed dental status (DMFT) and self-reported oral health of Turkish preadolescents was significantly poorer than the Finns`. A similar association occurred for well-being measures (height and weight, self-esteem), but not for school performance. Turkish preadolescents were more dentally anxious and reported lower mean values of toothbrushing self-efficacy and dietary self-efficacy than did Finns. The Turks less frequently reported recommended oral health behaviors (twice daily or more toothbrushing, sweet consumption on 2 days or less/week, decreased between-meal sweet consumption) than did the Finns. Turkish mothers reported less frequently dental health as being above average and recommended oral health behaviors as well as regular dental visits. Their mean values for dental anxiety was higher and self-efficacy on implementation of twice-daily toothbrushing were lower than those of the Finnish. Despite these differences between the Turks and Finns, the associations found in common for all preadolescents, regardless of cultural differences and different oral health care systems, assessed for the first time in a holistic framework, were as follows: There seems to be interrelation between oral health and general-well being (body height-weight measures, school performance, and self-esteem) among preadolescents: • The body height was an explanatory factor for dental health, underlining the possible common life-course factors for dental health and general well-being. • Better school performance, high levels of self-esteem and self-efficacy were interrelated and they contributed to good oral health. • Good school performance was a common predictor for twice-daily toothbrushing. Self-efficacy and maternal modelling have significant role for maintenance and improvement of both oral- and general health- related behaviors. In addition, there is need for integration of self-efficacy based approaches to promote better oral health. • All preadolescents with high levels of self-efficacy were more likely to report more frequent twice-daily toothbrushing and less frequent sweet consumption. • All preadolescents were likely to imitate toothbrushing and sweet consumption behaviors of their mothers. • High levels of self-efficacy contributed to low dental anxiety in various patterns in both groups. As a conclusion: • Many health-detrimental behaviors arise from the school age years and are unlikely to change later. Schools have powerful influences on children’s development and well-being. Therefore, oral health promotion in schools should be integrated into general health promotion, school curricula, and other activities. • Health promotion messages should be reinforced in schools, enabling children and their families to develop lifelong sustainable positive health-related skills (self-esteem, self-efficacy) and behaviors. • Placing more emphasis on behavioral sciences, preventive approaches, and community-based education during undergraduate studies should encourage social responsibility and health-promoting roles among dentists. Attempts to increase general well-being and to reduce oral health inequalities among preadolescents will remain unsuccessful if the individual factors, as well as maternal and societal influences, are not considered by psycho-social holistic approaches.

Male eating disorders and related traits : Genetic epidemiological study in Finnish twins

The aim of this study was to deepen the understanding of eating disorders, body image dissatisfaction and related traits in males by examining the epidemiology and genetic epidemiology of these conditions in representative population-based twin samples. The sample of Study I included adolescent twins from FinnTwin12 cohorts born 1983 87 and assessed by a questionnaire at ages 14 y (N=2070 boys, N=2062 girls) and 17 y (N=1857 boys, N=1984 girls). Samples of Studies II-V consisted of young adult twins born 1974-79 from FinnTwin16 cohorts (Study II N=1245 men, Study III N=724 men, Study IV N=2122 men, Study V N=2426 women and N=1962 men), who were assessed by a questionnaire at the age 22-28 y. In addition, 49 men and 526 women were assessed by a diagnostic interview. The overall response rates for both twin cohorts in all studies were 80-90%. In boys, mainly genetic factors (82%, 95% confidence interval [CI] 72-92) explained the covariation of self-esteem between the ages 14 y and 17 y, whereas in girls, environmental factors (69%, 95% CI 43-93) were the largest contributors. Of young men, 30% experienced high muscle dissatisfaction, while 12% used or had used muscle building supplements and/or anabolic steroids on a regular basis. Muscle dissatisfaction exhibited a robust association with the indicators of mental distress and a genetic component (42%, 95% CI 23-59) for its liability in this population was found. The variation of muscle-building substance use was primarily explained by the environmental factors. The incidence rate of anorexia nervosa in males for the age of 10-24 y was 15.7 (95% CI 6.6-37.8) per 100 000 person-years, and its lifetime prevalence by the young adulthood was 0.24% (95% CI 0.03-0.44). All detected probands with anorexia nervosa had recovered from eating disorders, but suffered from substantial psychiatric comorbidity, which manifested also in their co-twins. Additionally, male co-twins of the probands displayed significant dissatisfaction with body musculature, a male-specific feature of body dysmorphic disorder. All probands were from twin pairs discordant for eating disorders. Of the five male probands with anorexia nervosa, only one was from an opposite-sex twin pair. Among women from the opposite-sex pairs, the prevalence of DSM-IV or broad anorexia nervosa was no significantly different compared to that of the women from monozygotic pairs or from dizygotic same-sex pairs. The prevalence of DSM-IV or broad bulimia nervosa did not differ in opposite- versus same-sex female twin individuals either. In both sexes, the overall profile of indicators on eating disorders was rather similar between individuals from opposite-sex and same-sex pairs. In adolescence, development of self-esteem was differently regulated in boys compared to girls: this finding may have far-reaching implications on the etiology of sex discrepancy of internalizing and externalizing disorders. In young men, muscle dissatisfaction and muscle building supplement/steroid use were relatively common. Muscle dissatisfaction was associated with marked psychological distress such as symptoms of depression and disordered eating. Both genetic and environmental factors explained muscle dissatisfaction in the population, but environmental factors appeared to best explain the use of muscle-building substances. In this study, anorexia nervosa in boys and young men from the general population was more common, transient and accompanied by more substantial co-morbidity than previously thought. Co-twins of the probands with anorexia nervosa displayed significant psychopathology such as male specific symptoms of body dysmorphic disorder, but none of them had had an eating disorder: taken together, these traits are suggestive for an endophenotype of anorexia nervosa in males. Little evidence was found on that the risk for anorexia nervosa, bulimia nervosa, disordered eating or body dissatisfaction were associated with twin zygosity. Thus, it is unlikely that in utero femininization, masculinization or postnatal socialization according to the sex of the co-twin have a major influence on the later development of eating disorders or related traits.

α-Synuclein pathology in very elderly Finns : A population-based clinico-neuropathologic and molecular genetic study of Dementia with Lewy bodies

Populations in developed countries are ageing fast. The elderly have the greatest incidence of de-mentia, and thus the increase in the number of demented individuals, increases the immediate costs for the governments concerning healthcare and hospital treatment. Attention is being paid to disorders behind cognitive impairment with behavioural and psychological symptoms, which are enormous contributors to the hospital care required for the elderly. The highest dreams are in prevention; however, before discovering the tools for preventing dementia, the pathogenesis behind dementia disorders needs to be understood. Dementia with Lewy bodies (DLB), a relatively recently discovered dementia disorder compared to Alzheimer’s disease (AD), is estimated to account for up to one third of primary degenerative dementia, thus being the second most common cause of dementia in the elderly. Nevertheless, the impact of neuropathological and genetic findings on the clinical syndrome of DLB is not fully established. In this present series of studies, the frequency of neuropathological findings of DLB and its relation to the clinical findings was evaluated in a cohort of subjects with primary degenerative dementia and in a population-based prospective cohort study of individuals aged 85 years or older. α-synuclein (αS) immunoreactive pathology classifiable according to the DLB consensus criteria was found in one fourth of the primary degenerative dementia subjects. In the population-based study, the corresponding figure was one third of the population, 38% of the demented and one fifth of the non-demented very elderly Finns. However, in spite of the frequent discovery of αS pathology, its association with the clinical symptoms was quite poor. Indeed, the common clinical features of DLB, hypokinesia and visual hallucinations, associated better with the severe neurofibrillary AD-type pathology than with the extensive (diffuse neocortical) αS pathology when both types of pathology were taken into account. The severity of the neurofibrillary AD-type pathology (Braak stage) associated with the extent of αS pathology in the brain. In addition, the genetic study showed an interaction between tau and αS; common variation in the αS gene (SNCA) associated significantly with the severity of the neurofibrillary AD-type pathology and nominally significantly with the extensive αS pathology. Further, the relevance and temporal course of the substantia nigra (SN) degeneration and of the spinal cord αS pathology were studied in relation to αS pathology in the brain. The linear association between the extent of αS pathology in the brain and the neuron loss in SN suggests that in DLB the degeneration of SN proceeds as the αS pathology extends from SN to the neocortex instead of early destruction of SN seen in Parkinson’s disease (PD). Furthermore, the extent of αS pathology in the brain associated with the severity of αS pathology in the thoracic and sacral autonomic nuclei of the spinal cord. The thoracic αS pathology was more common and more severe compared to sacral cord, suggesting that the progress of αS pathology proceeds downwards from the brainstem towards the sacral spinal cord.

Search For Susceptibility Genes In Schizophrenia

Schizophrenia is a severe mental disorder affecting 0.4-1% of the population worldwide. It is characterized by impairments in the perception of reality and by significant social or occupational dysfunction. The disorder is one of the major contributors to the global burden of diseases. Studies of twins, families, and adopted children point to strong genetic components for schizophrenia, but environmental factors also play a role in the pathogenesis of disease. Molecular genetic studies have identified several potential positional candidate genes. The strongest evidence for putative schizophrenia susceptibility loci relates to the genes encoding dysbindin (DTNBP1) and neuregulin (NRG1), but studies lack impressive consistency in the precise genetic regions and alleles implicated. We have studied the role of three potential candidate genes by genotyping 28 single nucleotide polymorphisms in the DNTBP1, NRG1, and AKT1 genes in a large schizophrenia family sample consisting of 441 families with 865 affected individuals from Finland. Our results do not support a major role for these genes in the pathogenesis of schizophrenia in Finland. We have previously identified a region on chromosome 5q21-34 as a susceptibility locus for schizophrenia in a Finnish family sample. Recently, two studies reported association between the γ-aminobutyric acid type A receptor cluster of genes in this region and one study showed suggestive evidence for association with another regional gene encoding clathrin interactor 1 (CLINT1, also called Epsin 4 and ENTH). To further address the significance of these genes under the linkage peak in the Finnish families, we genotyped SNPs of these genes, and observed statistically significant association of variants between GABRG2 and schizophrenia. Furthermore, these variants also seem to affect the functioning of the working memory. Fetal events and obstetric complications are associated with schizophrenia. Rh incompatibility has been implicated as a risk factor for schizophrenia in several epidemiological studies. We conducted a family-based candidate-gene study that assessed the role of maternal-fetal genotype incompatibility at the RhD locus in schizophrenia. There was significant evidence for an RhD maternal-fetal genotype incompatibility, and the risk ratio was estimated at 2.3. This is the first candidate-gene study to explicitly test for and provide evidence of a maternal-fetal genotype incompatibility mechanism in schizophrenia. In conclusion, in this thesis we found evidence that one GABA receptor subunit, GABRG2, is significantly associated with schizophrenia. Furthermore, it also seems to affect to the functioning of the working memory. In addition, an RhD maternal-fetal genotype incompatibility increases the risk of schizophrenia by two-fold.

Genetics of Cardiovascular Disease: A Candidate Gene Study of USF1

Cardiovascular diseases (CVD) are major contributors to morbidity and mortality worldwide. Several interacting environmental, biochemical, and genetic risk factors can increase disease susceptibility. While some of the genes involved in the etiology of CVD are known, many are yet to be discovered. During the last few decades, scientists have searched for these genes with genome-wide linkage and association methods, and with more targeted candidate gene studies. This thesis investigates variation within the upstream transcription factor 1 (USF1) gene locus in relation to CVD risk factors, atherosclerosis, and incidence and prevalence of CVD. This candidate gene was first identified in Finnish families ascertained for familial combined hyperlipidemia, a common dyslipidemia predisposing to coronary heart disease. The gene is a ubiquitously expressed transcription factor regulating expression of several genes from lipid and glucose metabolism, inflammation, and endothelial function. First, we examined association between USF1 variants and several CVD risk factors, such as lipid phenotypes, body composition measures, and metabolic syndrome, in two prospective population cohorts. Our data suggested that USF1 contributes to these CVD risk factors at the population level. Notably, the associations with quantitative measurements were mostly detected among study subjects with CVD or metabolic syndrome, suggesting complex interactions between USF1 effects and the pathophysiological state of an individual. Second, we investigated how variation at the USF1 locus contributes to atherosclerotic lesions of the coronary arteries and abdominal aorta. For this, we used two study samples of middle-aged men with detailed measurements of atherosclerosis obtained in autopsy. USF1 variation significantly associated with areas of several types of lesions, especially with calcification of the arteries. Next, we tested what effect the USF1 risk variants have on sudden cardiac death and incidence of CVD. The atherosclerosis-associated risk variant increased the risk of sudden cardiac death of the same study subjects. Furthermore, USF1 alleles associated with incidence of CVD in the Finnish population follow-up cohorts. These associations were especially prominent among women, suggesting a sex specific effect, which has also been detected in subsequent studies. Finally, as some of the low-yield DNA samples of the Finnish follow-up study cohort needed to be whole-genome amplified (WGA) prior to genotyping, we evaluated whether the produced WGA genotypes were of good quality. Although the samples giving genotype discrepancies could not be detected before genotyping with standard laboratory quality control methods, our results suggested that enhanced quality control at the time of the genotyping could identify such samples. In addition, combining two WGA reactions into one pooled DNA sample for genotyping markedly reduced the number of discrepancies and samples showing them. In conclusion, USF1 seems to have a role in the etiology of CVD. Additional studies are warranted to identify functional variants and to study interactions between USF1 and other genetic or environmental factors. This USF1 study, and other studies with low DNA yield of some samples, can benefit from whole genome amplification of the low-yield samples prior to genotyping. Careful quality control procedures are, however, needed in WGA genotyping.

Fen ecosystem carbon gas dynamics in changing hydrological conditions

Northern peatlands are thought to store one third of all soil carbon (C). Besides the C sink function, peatlands are one of the largest natural sources of methane (CH4) to the atmosphere. Climate change may affect the C gas dynamics as well as the labile C pool. Because the peatland C sequestration and CH4 emissions are governed by high water levels, changes in hydrology are seen as the driving factor in peatland ecosystem change. This study aimed to quantify the carbon dioxide (CO2) and CH4 dynamics of a fen ecosystem at different spatial scales: plant community components scale, plant community scale and ecosystem scale, under hydrologically normal and water level drawdown conditions. C gas exchange was measured in two fens in southern Finland applying static chamber and eddy covariance techniques. During hydrologically normal conditions, the ecosystem was a CO2 sink and CH4 source to the atmosphere. Sphagnum mosses and sedges were the most important contributors to the community photosynthesis. The presence of sedges had a major positive impact on CH4 emissions while dwarf shrubs had a slightly attenuating impact. C fluxes varied considerably between the plant communities. Therefore, their proportions determined the ecosystem scale fluxes. An experimental water level drawdown markedly reduced the photosynthesis and respiration of sedges and Sphagnum mosses and benefited shrubs. Consequently, changes were smaller at the ecosystem scale than at the plant group scale. The decrease in photosynthesis and the increase in respiration, mostly peat respiration, made the fen a smaller CO2 sink. CH4 fluxes were significantly lowered, close to zero. The impact of natural droughts was similar to, although more modest than, the impact of the experimental water level drawdown. The results are applicable to the short term impacts of the water level drawdown and to climatic conditions in which droughts become more frequent.

Genetic aspects of outcome in kidney transplantation: cytokine and thrombosis associated candidate genes and gene expression biomarkers

Kidney transplantation (Tx) is the treatment of choice for end stage renal disease. Immunosuppressive medications are given to prevent an immunological rejection of the transplant. However, immunosuppressive drugs increase e.g. the risk of infection, cancer or nephrotoxicity. A major genetic contributors to immunological acceptance of the graft are human leukocyte antigen (HLA) genes. Also other non-HLA gene polymorphisms may predict the future risk of complications before Tx, possibly enabling individualised immunotherapy. Graft function after Tx is monitored using non-specific clinical symptoms and laboratory markers. The definitive diagnosis of graft rejection however relies on a biopsy of the graft. In the acute rejection (AR) diagnostics there is a need for an alternative to biopsy that would be an easily repeatable and simple method for regular use. Frequent surveillance of acute or subclinical rejection (SCR) may improve long-term function. In this thesis, associations between cytokine and thrombosis associated candidate genes and the outcome of kidney Tx were studied. Cytotoxic and co-stimulatory T lymphocyte molecule gene expression biomarkers for the diagnosis of the AR and the SCR were also investigated. We found that polymorphisms in the cytokine genes tumor necrosis factor and interleukin 10 (IL10) of the recipients were associated with AR. In addition, certain IL10 gene polymorphisms of the donors were associated with the incidence of cytomegalovirus infection and occurrence of later infection in a subpopulation of recipients. Further, polymorphisms in genes related to the risk of thrombosis and those of certain cytokines were not associated with the occurrence of thrombosis, infarction, AR or graft survival. In the study of biomarkers for AR, whole blood samples were prospectively collected from adult kidney Tx patients. With real-time quantitative PCR (RT-QPCR) gene expression quantities of CD154 and ICOS differentiated the patients with AR from those without, but not from the patients with other causes of graft dysfunction. Biomarkers for SCR were studied in paediatric kidney Tx patients. We used RT-QPCR to quantify the gene expression of immunological candidate genes in a low-density array format. In addition, we used RT-QPCR to validate the results of the microarray analysis. No gene marker differentiated patients with SCR from those without SCR. This research demonstrates the lack of robust markers among polymorphisms or biomarkers in investigated genes that could be included in routine analysis in a clinical laboratory. In genetic studies, kidney Tx can be regarded as a complex trait, i.e. several environmental and genetic factors may determine its outcome. A number of currently unknown genetic factors probably influence the results of Tx.