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  • Paloviita, Maritta (Suomen Pankki, 2009)
    The present study examines empirically the inflation dynamics of the euro area. The focus of the analysis is on the role of expectations in the inflation process. In six articles we relax rationality assumption and proxy expectations directly using OECD forecasts or Consensus Economics survey data. In the first four articles we estimate alternative Phillips curve specifications and find evidence that inflation cannot instantaneously adjust to changes in expectations. A possible departure of expectations from rationality seems not to be powerful enough to totally explain the persistence of euro area inflation in the New Keynesian framework. When expectations are measured directly, the purely forward-looking New Keynesian Phillips curve is outperformed by the hybrid Phillips curve with an additional lagged inflation term and the New Classical Phillips curve with a lagged expectations term. The results suggest that the euro area inflation process has become more forward-looking in the recent years of low and stable inflation. Moreover, in low inflation countries, the inflation dynamics have been more forward-looking already since the late 1970s. We find evidence of substantial heterogeneity of inflation dynamics across the euro area countries. Real time data analysis suggests that in the euro area real time information matters most in the expectations term in the Phillips curve and that the balance of expectations formation is more forward- than backward-looking. Vector autoregressive (VAR) models of actual inflation, inflation expectations and the output gap are estimated in the last two articles.The VAR analysis indicates that inflation expectations, which are relatively persistent, have a significant effect on output. However,expectations seem to react to changes in both output and actual inflation, especially in the medium term. Overall, this study suggests that expectations play a central role in inflation dynamics, which should be taken into account in conducting monetary policy.
  • Leppä, Johannes (Helsingin yliopisto, 2012)
    Atmospheric aerosol particles have various climate effects and adverse health effects, which both depend on the size and number concentration of the particles. Freshly-formed particles are not large enough to impact neither health nor climate and they are most susceptible to removal by collisions with larger pre-existing particles. Consequently, the knowledge of both the formation and the growth rate of particles are crucially important when assessing the health and climate effects of atmospheric new particle formation. The purpose of this thesis is to increase our knowledge of the dynamics of neutral and charged aerosol particles with a specific interest towards the particle growth rate and processes affecting the aerosol charging state. A new model, Ion-UHMA, which simulates the dynamics of neutral and charged particles, was developed for this purpose. Simple analytical formulae that can be used to estimate the growth rate due to various processes were derived and used to study the effects of charged particles on the growth rate. It was found that the growth rate of a freshly-formed particle population due to condensation and coagulation could be significantly increased when a considerable fraction of the particles are charged. Finally, recent data-analysis methods that have been applied to the aerosol charging states obtained from the measurements were modified for a charge asymmetric framework. The methods were then tested on data obtained from aerosol dynamics simulations. The methods were found to be able to provide reasonable estimates on the growth rate and proportion of particles formed via ion-induced nucleation, provided that the growth rate is high enough and that the charged particles do not grow much more rapidly than the neutral ones. A simple procedure for estimating whether the methods are suitable for analysing data obtained in specific conditions was provided. In this thesis, the dynamics of neutral and charged aerosol particles were studied in detail. Combined with the current field and chamber measurements of neutral and charged particles, the analytical tools provided here can be used to study the atmospheric new particle formation and growth more comprehensively and, eventually, to decrease the uncertainty related to climate effects of aerosol particles.
  • Skarp, Kari-Pekka (Helsingin yliopisto, 2014)
    The notion of actin in the nucleus has slowly garnered popularity over the decades transforming the protein from an obscure artefact into a target of extreme curiosity in that compartment. Actin has been associated with a whole spectrum of nuclear functions, which directly or undirectly connect the protein with the most important nuclear function, transcription. However, it is currently not known how actin enters the nucleus in the first place and whether the protein is subjected to constitutive transport between the two eukaryotic compartments. The question regarding nucleocytoplasmic shuttling of actin is further complicated by the fact that actin is near the nuclear pore complex size exclusion limit, which sets a physical barrier for passive diffusion but not active transport. To investigate the nature of actin transit between the nucleus and the cytoplasm we developed microscope assays to monitor the shuttling of fluorescently labeled particles in real time in living cells. Using our assays it was possible to quantitate nuclear actin import and export rates. This immediately revealed that actin constantly shuttles in steady state cells. We used fluorescent probes of various sizes to explore the limits of passive vs. active import and found that even if the size of the fluorescent actin construct is increased, it retains the import rate. This suggests an active mechanism is behind the nuclear import of actin, because passively traveling constructs slow down when size increases as shown by controls. Longer observations of nuclear import revealed that nuclear actin exists in at least three pools of different motility and the largest one exhibits retarded exchange rates with the environment. This is consistent with the reports of actin bound to various nuclear complexes, which may render the actins in question less mobile. We were also able to clarify the status of actin export, where two export receptors have been reported. By using a small molecule inhibitor, we showed that CRM1 does not participate in the export of actin, which at least during steady state seems to fall exclusively in the domain of exportin 6. Next we identified the components of active import machinery by using RNAi vs. exportin 6 and suspected import factors. We found that actin is imported in complex with importin 9 and unphosphorylated cofilin and the process is dependent on Ran. We then showed that RNA polymerase II dependent transcription requires a suitable amount of actin in the nucleus or it is disrupted. Finally, we wanted to investigate which cellular features might correlate with the transport rates of actin and how actin shuttling is conducted in cells of varying amount of actin in the 2 nucleus in relation to cytoplasm (N/C ratio). We found that factors such as the size or shape of the nucleus or cytoplasm or the ratio of their sizes does not affect the import or export rates of actin. Instead, we made the surprising discovery the the N/C ratio of actin inversely correlates with both export and import. This means that the fastest shuttling rates can be found in cells with least actin in the nucleus while in cells of high amount of actin in the nucleus, the transport is slow. The latter situation suggests the nucleus is filled actin, which is somehow made export incompetent, perhaps by associating with nuclear complexes. To explore the matter further, we performed studies on the motility of nuclear and cytoplasmic actin pools. However, we found no relation with high N/C ratio of actin and the size of the G-actin pool. This suggests that the primary mode of regulation of nucleocytoplasmic shuttling does not take place through manipulating the size of the global G-actin pool.
  • Hölttä, Teemu (Helsingin yliopisto, 2005)
  • Zhang, Lei (Helsingin yliopisto, 2010)
    Dyslipidaemia, a major risk factor of cardiovascular disease (CVD), is prevalent not only in diabetic patients but also in individuals with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). The aims of this study were: 1) to investigate lipid levels in relation to glucose in European (Study I) and Asian (Study II) populations without a prior history of diabetes; 2) to study the ethnic difference in lipid profiles controlling for glucose levels (Study III); 3) to estimate the relative risk for cardiovascular mortality (Study IV) and morbidity (Study V) associated with dyslipidaemia in individuals with different glucose tolerance status. Data of 15 European cohorts with 19 476 subjects (I and III) and 13 Asian cohorts with 19 763 individuals (II and III) from 21 countries aged 25-89 years, without a prior history of diabetes at enrollment, representing Asian Indian, Chinese, European, Japanese and Mauritian Indian, were compared. The lipid-CVD relationship was studied in 14 European cohorts of 17 763 men and women which provided with follow-up data on vital status, with 871 CVD deaths occurred during the average 10-year follow-up (IV). The impact of dyslipidaemia on incidence of coronary heart disease (CHD) in persons with different glucose categories (V) was further evaluated in 6 European studies, with 9087 individuals free of CHD at baseline and 457 developed CHD during follow-up. Z-scores of each lipid component were used in the data analysis (I, II, IV and V) to reduce the differences in methodology between studies. Analyses of cardiovascular mortality and morbidity were performed using Cox proportional hazards regression analysis adjusting for potential confounding factors. Within each glucose category, fasting plasma glucose (FPG) levels were correlated with increasing levels of triglycerides (TG), total cholesterol (TC), TC to high-density lipoprotein (HDL) ratio and non-HDL cholesterol (non-HDL-C) (p<0.05 in most of the ethnic groups) and inversely associated with HDL-C (p<0.05 in some, but not all, of the populations). The association of lipids with 2-h plasma glucose (2hPG) followed a similar pattern as that for the FPG, except the stronger association of HDL-C with 2hPG. Compared with Central & Northern (C & N) Europeans, multivariable adjusted odd ratios (95% CIs) for having low HDL-C were 4.74 (4.19-5.37), 5.05 (3.88-6.56), 3.07 (2.15-4.40) and 2.37 (1.67-3.35) in Asian Indian men but 0.12 (0.09-0.16), 0.07 (0.04-0.13), 0.11 (0.07-0.20) and 0.16 (0.08-0.32) in Chinese men who had normoglycaemia, prediabetes, undiagnosed and diagnosed diabetes, respectively. Similar results were obtained for women. The prevalence of low HDL-C remained higher in Asian Indians than in others even in individuals with LDL-C < 3 mmol/l. Dyslipidaemia was associated with increased CVD mortality or CHD incidence in individuals with isolated fasting hyperglycaemia or IFG, but not in those with isolated post-load hyperglycaemia or IGT. In conclusion, hyperglycaemia is associated with adverse lipid profiles in Europeans and Asians without a prior history of diabetes. There are distinct patterns of lipid profiles associated with ethnicity regardless of the glucose levels, suggesting that ethnic-specific strategies and guidelines on risk assessment and prevention of CVD are required. Dyslipidaemia predicts CVD in either diabetic or non-diabetic individuals defined based on the fasting glucose criteria, but not on the 2-hour criteria. The findings may imply considering different management strategies in people with fasting or post-load hyperglycaemia.
  • E. 
    Aho, Lauri E. (1930)
  • E. 
    Lohikoski, Virpi (1998)
  • Lindqvist, Ulla (2008)
    The purpose of this study is to describe and evaluate the work of early intervention and family support in Family Centres of Helsinki City Social Services Department. The subject matter in this study is approached by using community social work perspective. The research data consists of descriptions of early intervention and family support working models. Descriptions have been gathered from the workers of play parks, social and family work, families with children home service, family houses and groups and projects in two phases: first by a questionnaire and thereafter worker joint development process. This study is a part of the development process of early intervention and family support in Family Centres. The data was analysed by applying theory engaged examination and content analysis. Evaluation method is description and the purpose is to create an overview the work of early intervention and family support and its development needs. The approach to research is development evaluation. The workers described in the questionnaire 393 different working models. Based on analysis working methods of direct client work were defined as follows: family work, group work, community work, multicultural work and information about the services. Working methods of indirect client work were defined as multiprofessional network and strengthening of the working methods of early intervention and family support. Based on the questionnaire workers saw supporting parenthood and strengthening of social networks needs for the work. Experienced results of the working methods were positive and their achievements were experienced in family and group work. Based on workers experience working methods close to basic work were considered to be effective. Workers evaluate that the working methods brought a change to client's life situation (medium 8,31 on scale 1-10). The descriptions prepared in the development process examine early intervention and family support in three levels: community, department and worker/working place. Local co-operation and group work were described by all functions. This study investigates also the descriptions of the workers from play parks from the community and community social work perspective. Parks are described as spaces of community, where participation and empowerment is made possible. The work of early intervention and family support is not a uniform collection of working methods which would be similar to all functions. All functions do it by taking into account the basic work and its specific features. Based on the analysis of descriptions I suggest looking at the early intervention and family support from developmental, social and operational point of view. Operational viewpoint is intervention and support on individual and community level. Through these elements both universal and selective needs of children and their families is visible in early intervention and family support. The changes in working environment have an impact on the development of the work. In this study four development strategies have been created from community social work basis. In these strategies the aim, elements and methods of work have been combined. Strategies are proactive and preventive work, services close to community, work centred on the social network and shared responsibility of practitioners and citizens.
  • Rosengård-Bärlund, Milla (Helsingin yliopisto, 2014)
    Diabetic autonomic neuropathy is a serious complication, associated with increased risk of morbidity and mortality, but it is perhaps the least understood of the diabetic complications. The challenge lies in the early diagnosis of this often subclinical condition, in the time window when it would still be treatable. Notably, when detected with the current diagnostic tools, diabetic autonomic neuropathy has been considered as the result of irreversible nerve damage. Reduced baroreflex sensitivity (BRS) is a sensitive marker of autonomic dysfunction, and importantly, also a prognostic marker in cardiovascular medicine. In addition to diabetes, abnormalities in the BRS also occur in conditions characterized by functional autonomic abnormalities such as myocardial infarction, heart failure, and hypertension. Accordingly, we hypothesized that early autonomic dysfunction in type 1 diabetes, as demonstrated by reduced BRS, is functional. The aim of this thesis was to elucidate the early markers of autonomic dysfunction in patients with type 1 diabetes of various durations. We reasoned that if BRS in patients with type 1 diabetes responds to slow, deep breathing, a manoeuvre shown to reduce sympathetic activity, or responds to oxygen administration, such a finding would support a functional aetiology. We also studied whether autonomic dysfunction, as established by reduced BRS, progresses alongside increasing diabetes duration to a stage where it is no longer improved by a functional manoeuvre. Moreover, we aimed to elucidate the role of BRS as a predictor of increased blood pressure (BP) level during a 5-year follow-up. We studied 117 patients with short (8.9±0.1 yrs) and 37 patients with long duration (33.7±0.5 yrs) type 1 diabetes, and a total of 73 age- and gender-matched, healthy control participants. Twelve heart-transplanted patients served as a model of cardiac denervation. An autonomic score was calculated from autonomic function tests. Spectral analysis of heart rate variability (HRV), blood pressure variability (BPV), and BRS came from recordings during normal (15/min) and slow, deep (6/min) controlled breathing. Of those with short-duration type 1 diabetes, 96 subjects were studied during a prospective visit by similar autonomic assessment as at baseline but in addition, with BRS assessed during inhalation of oxygen. In a total of 80 patients, we compared autonomic indices and ambulatory BP at baseline and follow-up. BRS was already reduced in patients with short-duration type 1 diabetes, but even more reduced in those with long duration or with increasing autonomic involvement. Slow breathing elevated the BRS to the level of control subjects at a normal breathing rate (15/min) in all patients except in those with an abnormal autonomic score. BRS also increased with oxygen during spontaneous breathing in diabetic but not in control participants, and with oxygen the difference in BRS was no longer significant. Slow breathing in normoxia restored the BRS to a similar extent as did oxygen. In the follow-up study, spontaneous BRS declined over time, but the change was not significant when adjusted for time of follow-up. Low BRS at baseline did not advance to cardiovascular autonomic neuropathy (CAN) but predicted an increase in night-time systolic BP. Furthermore, the BRS response to deep breathing at baseline predicted the increase found in 24-hour ambulatory BP. The results of this thesis indicate that even after long-duration diabetes, any abnormal BRS is at least in part of functional origin. The increased baroreflex response to oxygen supports the hypothesis of a functional reduction in parasympathetic activity occurring in patients with type 1 diabetes. The follow-up study showed that the decline in spontaneous BRS over time in patients with type 1 diabetes seems to be mainly due to normal ageing. Although early autonomic dysfunction seems functional and does not necessarily develop into autonomic neuropathy during a 5-year follow-up, the BRS and the response to deep breathing at baseline are associated with a future increase in BP. More research and a longer follow-up time will be required to fully clarify the prognostic significance of BRS in type 1 diabetes.
  • Mohebbi, Simin Z. (Helsingfors universitet, 2008)
    The present study assessed the prevalence of and risk factors for Early Childhood Caries (ECC) in children 12- to 36- month-old and evaluated the impacts of an educational intervention on ECC prevention in the 12- to 15-month-old cohort. The target population included 12- to 36-month-olds (n = 504) and their mothers attending the vaccination offices of 18 randomly selected public health centers of Tehran city. The mother was first interviewed by a structured questionnaire covering background factors, feeding habits, daytime sugar intake, mother’s and child’s oral cleaning habits, and mother’s perception toward her ability to maintain the child’s oral hygiene; then the child’s clinical dental examination was carried out covering caries experience and dental plaque status. In addition, the 12- to 15-month-olds (n = 242) were assigned to a six-month interventional study. The 18 health centers were randomly allocated into two groups for intervention and one for control. The mothers in the intervention groups received education on caries prevention from the vaccination staff with extra motivation as reminder phone calls in one of the intervention groups. The outcome was measured as differences in increments of enamel and dentinal caries. The results showed that the prevalence of ECC was rather high (3%-26%) in the three age groups, and almost all dmft was due to untreated caries. The majority of the children showed visible plaque on central upper incisors. Oral cleaning on a daily basis was reported for just 68% of mothers and 39% of children. The frequency of oral cleaning and good oral hygiene of the child were directly proportional to the mother’s own toothbrushing frequency. Of the children, 98% were solely or partly breastfed. ECC was more likely to occur among those for whom the burden of milk-bottle feeding at night existed (OR = 4.9), while breastfeeding per se, its duration, and its nighttime burden were not related to ECC. The indicator of daytime sugar intake also did not show a clear relationship with ECC. The educational intervention applying a pamphlet with some extra motivation and implemented by non-dental staff of public health centers appeared to be successful in preventing caries increments. To improve oral health status among the young children in countries with a developing oral health system, community-based oral health educational programs should be established by involving non-dental staff of health settings who are more frequently in contact with these children. Parents should be encouraged to realize that they play the dominant role in the oral health care of their children. Parents’ own oral health behaviors should be emphasized in dental and general health settings.
  • Toljamo, Tuula (Helsingin yliopisto, 2012)
    Chronic obstructive pulmonary disease (COPD) is an under-diagnosed and life-threatening progressive disease. Early symptoms of COPD include excessive sputum production and chronic cough. The primary risk factor of this disease in the western world is smoking. COPD is confirmed by spirometry, which does not totally reveal reversible airway obstruction. This study, conducted mainly in the Northern Finland, aimed to assess 1) smoking habits and smoking cessation in healthy middle-aged and young adults, 2) the prevalence of COPD and role of spirometry and prolonged respiratory symptoms in the diagnosis of COPD of smoking middle-aged adults, 3) the association of symptoms of chronic bronchitis with smoking habits in young adult males, and 4) to seek and to identify new potential biomarkers related to early COPD using non-hypothesis driven non-biased proteomics. A two-year prospective study included two visits to evaluate symptoms in healthy cigarette smokers, to screen new COPD cases and to assess the success of smoking cessation using motivational counselling and pharmacological therapies. In addition, a quantitative cross-sectional questionnaire survey was conducted in 1163 male conscripts during their military service in Northern Finland. A lung tissue proteomic approach was used to identify new COPD biomarkers. Spirometry revealed COPD by GOLD criteria in 11,0% and by national criteria in 15.3 % of originally asymptomatic chronic smokers. Further, chronic cough or sputum production was detected in 62.0% of the participants. After two years, 23.3% of adults had succeeded in quitting smoking. In young adults, 46.5% were daily smokers. The prevalence of self-reported chronic cough and sputum production was high in daily smokers (40.7%). The majority (60.2%) of the daily young smokers had made quit attempts and 46.9% of them had used nicotine replacement therapy (NRT). Based on the lung tissue proteomics, surfactant protein A (SP-A) was one of the most highly elevated spots in the COPD lung. The plasma SP-A concentration was higher both in chronic smokers and in COPD as compared to the non-smokers, and declined significantly during 2-year follow-up in those who succeeded to quit smoking compared to those who continued to smoke. To conclude there is remarkable burden of chronic bronchitis and COPD in the groups of chronic smokers who considered themselves as healthy. Motivational counselling seems to be successful, since over 23% of the adult smokers succeeded in stopping smoking. SP-A is a potential new biomarker for COPD although it needs further evaluation.
  • Gao, Weiguo (Helsingin yliopisto, 2010)
    Objectives of this study were to determine secular trends of diabetes prevalence in China and develop simple risk assessment algorithms for screening individuals with high-risk for diabetes or with undiagnosed diabetes in Chinese and Indian adults. Two consecutive population based surveys in Chinese and a prospective study in Mauritian Indians were involved in this study. The Chinese surveys were conducted in randomly selected populations aged 20-74 years in 2001-2002 (n=14 592) and 35-74 years in 2006 (n=4416). A two-step screening strategy using fasting capillary plasma glucose (FCG) as first-line screening test followed by standard 2-hour 75g oral glucose tolerance tests (OGTTs) was applied to 12 436 individuals in 2001, while OGTTs were administrated to all participants together with FCG in 2006 and to 2156 subjects in 2002. In Mauritius, two consecutive population based surveys were conducted in Mauritian Indians aged 20-65 years in 1987 and 1992; 3094 Indians (1141 men), who were not diagnosed as diabetes at baseline, were reexamined with OGTTs in 1992 and/or 1998. Diabetes and pre-diabetes was defined following 2006 World Health Organization/ International Diabetes Federation Criteria. Age-standardized, as well as age- and sex-specific, prevalence of diabetes and pre-diabetes in adult Chinese was significantly increased from 12.2% and 15.4% in 2001 to 16.0% and 21.2% in 2006, respectively. A simple Chinese diabetes risk score was developed based on the data of Chinese survey 2001-2002 and validated in the population of survey 2006. The risk scores based on β coefficients derived from the final Logistic regression model ranged from 3 – 32. When the score was applied to the population of survey 2006, the area under operating characteristic curve (AUC) of the score for screening undiagnosed diabetes was 0.67 (95% CI, 0.65-0.70), which was lower than the AUC of FCG (0.76 [0.74-0.79]), but similar to that of HbA1c (0.68 [0.65-0.71]). At a cut-off point of 14, the sensitivity and specificity of the risk score in screening undiagnosed diabetes was 0.84 (0.81-0.88) and 0.40 (0.38-0.41). In Mauritian Indian, body mass index (BMI), waist girth, family history of diabetes (FH), and glucose was confirmed to be independent risk predictors for developing diabetes. Predicted probabilities for developing diabetes derived from a simple Cox regression model fitted with sex, FH, BMI and waist girth ranged from 0.05 to 0.64 in men and 0.03 to 0.49 in women. To predict the onset of diabetes, the AUC of the predicted probabilities was 0.62 (95% CI, 0.56-0.68) in men and 0.64(0.59-0.69) in women. At a cut-off point of 0.12, the sensitivity and specificity was 0.72(0.71-0.74) and 0.47(0.45-0.49) in men; and 0.77(0.75-0.78) and 0.50(0.48-0.52) in women, respectively. In conclusion, there was a rapid increase in prevalence of diabetes in Chinese adults from 2001 to 2006. The simple risk assessment algorithms based on age, obesity and family history of diabetes showed a moderate discrimination of diabetes from non-diabetes, which may be used as first line screening tool for diabetes and pre-diabetes, and for health promotion purpose in Chinese and Indians.
  • Hukkinen, Katja (Helsingin yliopisto, 2007)
    The greatest effect on reducing mortality in breast cancer comes from the detection and treatment of invasive cancer when it is as small as possible. Although mammography screening is known to be effective, observer errors are frequent and false-negative cancers can be found in retrospective studies of prior mammograms. In the year 2001, 67 women with 69 surgically proven cancers detected at screening in the Mammography Centre of Helsinki University Hospital had previous mammograms as well. These mammograms were analyzed by an experienced screening radiologist, who found that 36 lesions were already visible in previous screening rounds. CAD (Second Look v. 4.01) detected 23 of these missed lesions. Eight readers with different kinds of experience with mammography screening read the films of 200 women with and without CAD. These films included 35 of those missed lesions and 16 screen-detected cancers. CAD sensitivity was 70.6% and specificity 15.8%. Use of CAD lengthened the mean time spent for readings but did not significantly affect readers sensitivities or specificities. Therefore the use of applied version of CAD (Second Look v. 4.01) is questionable. Because none of those eight readers found exactly same cancers, two reading methods were compared: summarized independent reading (at least a single cancer-positive opinion within the group considered decisive) and conference consensus reading (the cancer-positive opinion of the reader majority was considered decisive). The greatest sensitivity of 74.5% was achieved when the independent readings of 4 best-performing readers were summarized. Overall the summarized independent readings were more sensitive than conference consensus readings (64.7% vs. 43.1%) while there was far less difference in mean specificities (92.4% vs. 97.7%). After detecting suspicious lesion, the radiologist has to decide what is the most accurate, fast, and cost-effective means of further work-up. The feasibility of FNAC and CNB in the diagnosis of breast lesions was compared in non-randomised, retrospective study of 580 (503 malignant) breast lesions of 572 patients. The absolute sensitivity for CNB was better than for FNAC, 96% (206/214) vs. 67% (194/289) (p < 0.0001). An additional needle biopsy or surgical biopsy was performed for 93 and 62 patients with FNAC, but for only 2 and 33 patients with CNB. The frequent need of supplement biopsies and unnecessary axillary operations due to false-positive findings made FNAC (294 ) more expensive than CNB (223 ), and because the advantage of quick analysis vanishes during the overall diagnostic and referral process, it is recommendable to use CNB as initial biopsy method.
  • Ylihärsilä, Hilkka (Helsingin yliopisto, 2008)
    Theory of developmental origins of adult health and disease proposes that experiences during critical periods of early development may have consequences on health throughout a lifespan. Thesis studies aimed to characterize associations between early growth and some components of the metabolic syndrome cluster. Participants belong to two epidemiological cohorts with data on birth measurements and, for the younger cohort, on serial recordings of weight and height during childhood. They were born as singletons between 1924-33 and 1934-44 in the Helsinki University Central Hospital, and 500 and 2003 of them, respectively, attended clinical studies at the age of 65-75 and 56-70 years, respectively. In the 65-75 year old men and women, the well-known inverse relationship between birth weight and systolic blood pressure (SBP) was confined to people who had established hypertension. Among them a 1-kg increase in birth weight was associated with a 6.4-mmHg (95% CI: 1.0 to 11.9) decrease in SBP. This relationship was further confined to people with the prevailing Pro12Pro polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) gene. People with low birth weight were more likely to receive angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARB, p=0.03), and, again, this relationship was confined to the carriers of the Pro12Pro (p=0.01 for interaction). These results suggest that the inverse association between birth weight and systolic BP becomes focused in hypertensive people because pathological features of BP regulation, associated with slow fetal growth, become self-perpetuating in adult life. Insulin resistance of the Pro12Pro carriers with low birth weight may interact with the renin-angiotensin system leading to raised BP levels. Habitual physical activity protected men and women who were small at birth, and thus at increased risk for the development of type 2 diabetes, against glucose intolerance more strongly. Among subjects with birth weight ≤3000 g, the odds ratio (OR) for glucose intolerance was 5.2 (95% CI: 2.1 to 13) in those who exercised less than 3 times per week compared to regular exercisers; in those who scored their exercise light compared with moderate exercisers (defined as comparable to brisk walking) the OR was 3.5 (1.5 to 8.2). In the 56-70 year old men a 1 kg increase in birth weight corresponded to a 4.1 kg (95% CI: 3.1 to 5.1) and in women to a 2.9 kg (2.1 to 3.6) increase in adult lean mass. Rapid gain in body mass index (BMI), i.e. crossing from an original BMI percentile to a higher one, before the age of 2 years increased adult lean mass index (LMI, lean mass/height squared) without excess fat accumulation whereas rapid gain in BMI during later childhood, despite the concurrent rise in LMI, resulted in a relatively higher increase in adult body fat mass. These findings illustrate how genes, the environment and their interactions, early growth patterns, and adult lifestyle modify adult health risks which originate from early life.
  • Perälä, Mia-Maria (Helsingin yliopisto, 2014)
    Epidemiological studies have shown that low birth weight and slow growth during infancy predict an increased risk of metabolic diseases, including type 2 diabetes and cardiovascular disease, in adult life. Unhealthy dietary habits are also closely linked with these diseases. However, few results are available on whether dietary habits play a role in the association between birth size and disease risk in later life. The aim of this thesis was to determine whether body size at birth is associated with food and nutrient intake later in life and whether birth weight modifies the relationship between salt intake and blood pressure. In addition, the impact of early growth on postprandial metabolism was examined. These studies included 2003 men and women born in Helsinki between 1934 and 1944 with detailed information of their birth weight and childhood growth. They participated in a clinical examination between 2001 and 2004. In the clinic, their weight, height and blood pressure were measured and they filled a validated food-frequency questionnaire. Of those who attended the clinical study, 12 obese individuals with a slow increase in body mass index (BMI) during the first year of life and 12 BMI- and age-matched controls were recruited to participate in the postprandial studies. Each participant consumed six different test meals in random order. Body size at birth was positively associated with consumption of fruits and berries and intake of carbohydrates, sugars and fibre, and inversely associated with intake of fat. Salt intake was related to systolic blood pressure among low birth weight participants (birth weight ≤ 3050 g) but not among participants whose birth weight was > 3050 g. Salt intake was not significantly associated with diastolic blood pressure, either in the low birth weight or high birth weight groups. Early growth affected the postprandial responses, and insulin and triglyceride responses were significantly higher in the group that grew slowly during early life than in the controls. Individuals with slow early growth also showed higher appetite regulatory hormone peptide YY responses than did the controls. This study showed that individuals born with small body size may be programmed towards unhealthy dietary habits. In addition, they are sensitive to the blood pressure-raising effect of salt and therefore, may especially benefit from a reduction in salt intake. Slow growth during early life adversely affects postprandial insulin and triglyceride responses. Unhealthy dietary habits and elevated postprandial responses may be one underlying mechanism explaining the increased risk of metabolic diseases associated with nonoptimal early growth. Early growth may also alter appetite regulatory hormone secretion, which could be one explanation why individuals born small or who grow slowly during infancy are unlikely to become obese in later life.