Nocturnal Transcutaneous Carbon Dioxide and Early Changes in Atherosclerosis in Pre- and Postmenopausal Women

The risk of cardiovascular diseases and sleep-disordered breathing increases after menopause. This cross-sectional study focuses on overnight transcutaneous carbon dioxide (TcCO₂) measurements and their power to predict changes in the early markers of cardiovascular and metabolic diseases. The endothelial function of the brachial artery, the intima-media thickness of the carotid artery, blood pressure, glycosylated hemoglobin A1C and plasma levels of cholesterols and triglycerides were used as markers of cardiovascular and metabolic diseases. The study subjects consisted of healthy premenopausal women of 46 years of age and postmenopausal women of 56 years of age. From wakefulness to sleep, the TcCO₂ levels increased more in postmenopausal women than in premenopausal women. In estrogen-users the increase in TcCO₂ levels was even more pronounced than in other postmenopausal women. From the dynamic behaviour of the nocturnal TcCO₂ signal, several important features were detected. These TcCO₂ features had a remarkable role in the prediction of endothelial dysfunction and thickening of the carotid wall in healthy premenopausal women. In addition, these TcCO₂ features were linked with blood pressure, lipid profile and glucose balance in postmenopausal women. The nocturnal TcCO₂ profile seems to contain significant information, which is associated with early changes in cardiovascular diseases in middle-aged women. TcCO₂ might not only measure the tissue carbon dioxide levels, but the TcCO₂ signal variation may also reflect peripheral vasodynamic events caused by increased sympathetic activity during sleep.

Early nutritional determinants in cardio-metabolic programming – A prospective randomized controlled dietary intervention study

Western societies have been faced with the fact that overweight, impaired glucose regulation and elevated blood pressure are already prevalent in pediatric populations. This will inevitably mean an increase in later manifestations of cardio-metabolic diseases. The dilemma has been suggested to stem from fetal life and it is surmised that the early nutritional environment plays an important role in the process called programming. The aim of the present study was to characterize early nutritional determinants associating with cardio-metabolic risk factors in fetuses, infants and children. Further, the study was designated to establish whether dietary counseling initiated in early pregnancy can modify this cascade. Healthy mother-child pairs (n=256) participating in a dietary intervention study were followed from early pregnancy to childhood. The intervention included detailed dietary counseling by a nutritionist targeting saturated fat intake in excess of recommendations and fiber consumption below recommendations. Cardio-metabolic programming was studied by characterizing the offspring’s cardio-metabolic risk factors such as over-activation of the autonomic nervous system, elevated blood pressure and adverse metabolic status (e.g. serum high split proinsulin concentration). Fetal cardiac sympathovagal activation was measured during labor. Postnatally, children’s blood pressure was measured at six-month and four-year follow-up visits. Further, infants’ metabolic status was assessed by means of growth and serum biomarkers (32-33 split proinsulin, leptin and adiponectin) at the age of six months. This study proved that fetal cardiac sympathovagal activity was positively associated with maternal pre-pregnancy body mass index indicating adverse cardio-metabolic programming in the offspring. Further, a reduced risk of high split proinsulin in infancy and lower blood pressure in childhood were found in those offspring whose mothers’ weight gain and amount and type of fats in the diet during pregnancy were as recommended. Of note, maternal dietary counseling from early pregnancy onwards could ameliorate the offspring’s metabolic status by reducing the risk of high split proinsulin concentration, although it had no effect on the other cardio-metabolic markers in the offspring. At postnatal period breastfeeding proved to entail benefits in cardio-metabolic programming. Finally, the recommended dietary protein and total fat content in the child’s diet were important nutritional determinants reducing blood pressure at the age of four years. The intrauterine and immediate postnatal period comprise a window of opportunity for interventions aiming to reduce the risk of cardio-metabolic disorders and brings the prospect of achieving health benefits over one generation.

Late effects of cancer at a young age: Registry-based studies of the health of cancer patients and their off-spring

Modern cancer therapy has resulted in increased survival among patients diagnosed with cancer at a young age. These improvements have led to the investigation of late morbidity and mortality associated with cancer and its treatments. The aim of this study was to evaluate late effects of cancer treated at a young age on the health of patients and their offspring. Utilising the nationwide population-based registries in Finland, we evaluated the risk of hypothyroidism and the probability of parenthood in cancer survivors as well as preterm birth, neonatal outcomes, and the risk of cancer among offspring of patients. The survivor cohort, identified from the Finnish Cancer Registry, consisted of 25,784 cancer patients diag-nosed between ages 0 and 34 in 1953–2004. By linkage to the population register, siblings of these patients were identified for comparison. The prevalence of hypothyroidism was higher among former childhood cancer (aged 0–16) patients than in the general population. The probability of parenthood following early onset cancer was overall significantly reduced compared to siblings. Offspring of female cancer survivors were at an increased risk of preterm birth, this risk being highest among patients diagnosed in childhood and early adulthood (aged 20–34 years). The offspring were not, however, at a significantly increased risk of neonatal death or stillbirth, though they were more likely to need monitoring or intensive care in the neonatal period. The risk of sporadic cancer among offspring of male and female cancer survivors was not elevated in comparison to the general population. The study showed that former cancer patients are at risk of certain adverse endocrine and reproductive health outcomes and should be followed for timely intervention. The offspring of cancer survivors do not appear to be at risk for adverse health outcomes.

Cognitive Development of Very Low Birth Weight Children from Infancy to Pre-school Age

The survival of preterm born infants has increased but the prevalence of long-term morbidities has still remained high. Preterm born children are at an increased risk for various developmental impairments including both severe neurological deficits as well as deficits in cognitive development. According to the literature the developmental outcome perspective differs between countries, centers, and eras. Definitions of preterm infant vary between studies, and the follow-up has been carried out with diverse methods making the comparison less reliable. It is essential to offer parents upto-date information about the outcome of preterm infants born in the same area. A centralized follow-up of children at risk makes it possible to monitor the consequences of changes in the treatment practices of hospitals on developmental outcome. This thesis is part of a larger regional, prospective multidisciplinary follow-up project entitled “Development and Functioning of Very Low Birth Weight Infants from Infancy to School Age” (PIeniPAinoisten RIskilasten käyttäytyminen ja toimintakyky imeväisiästä kouluikään, PIPARI). The thesis consists of four original studies that present data of very low birth weight (VLBW) infants born between 2001 and 2006, who are followed up from the neonatal period until the age of five years. The main outcome measure was cognitive development and secondary outcomes were significant neurological deficits (cerebral palsy, CP, deafness, and blindness). In Study I, the early crying and fussing behavior of preterm infants was studied using parental diaries, and the relation of crying behavior and cognitive and motor development at the age of two years was assessed. In Study II, the developmental outcome (cognitive, CP, deafness, and blindness) at the age of two years was studied in relation to demographic, antenatal, neonatal, and brain imaging data. Development was studied in relationship to a full-term born control group born in the same hospital. In Study III, the stability of cognitive development was studied in VLBW and full-term groups by comparing the outcomes at the ages of two and five years. Finally, in Study IV the precursors of reading skills (phonological processing, rapid automatized naming, and letter knowledge) were assessed for VLBW and full-term children at the age of five years. Pre-reading skills were studied in relation to demographic, antenatal, neonatal, and brain imaging data. The main findings of the thesis were that VLBW infants who fussed or cried more in the infancy were not at greater risk for problems in their cognitive development. However, crying was associated with poorer motor development. The developmental outcome of the present population was better that has been reported earlier and this improvement covered also cognitive development. However, the difference to fullterm born peers was still significant. Major brain pathology and intestinal perforation were independent significant risk factors for adverse outcome, also when several individual risk factors were controlled for. Cognitive development at the age of two years was strongly related with development at the age of five years, stressing the importance of the early assessment, and the possibility for early interventions. Finally, VLBW children had poorer pre-reading skills compared with their full-term born peers, but the IQ was an important mediator even when children with mental retardation were excluded from the analysis. The findings suggest that counseling parents about the developmental perspectives of their preterm infant should be based on data covering the same birth hospital. Neonatal brain imaging data and neonatal morbidity are important predictors for developmental outcome. The findings of the present study stress the importance of both short-term (two years) and long-term (five years) follow-ups for the individual, and for improving the quality of care.

Administration of Bifidobacterium animalis subsp. lactis BB-12 and xylitol with a novel pacifier in early childhood

Probiotic bifidobacteria are used in the prevention and treatment of childhood diseases. On the other hand, these bacteria are also connected to dental caries. The purpose of the present work was to test a food supplement containing Bifidobacterium animalis subsp. lactis BB-12 (B. lactis BB-12) and xylitol, and to investigate its health effects, properties and safety when used in a novel pacifier in early childhood. In a double-blind, placebo-controlled trial, newborn infants (n=163) were assigned randomly to receive B. lactis BB-12, xylitol, or sorbitol from the age of 1– 2 monthsto 2 years with a pacifier or a spoon. Children were followed up to four years of age. A part of the parents participating in the clinical trial evaluated the feasibility of the novel administration method. The pattern of tablet release from the pouch of the pacifier was tested in adults. The food supplement tablet containing B. lactis BB-12 and xylitol could be delivered in a safe and controlled way with the novel pacifier. The early administration of B. lactis BB-12 did not result in permanent oral colonization of this probiotic or affect the colonization of mutans streptococci in early childhood. Moreover, B. lactis BB-12 did not increase the occurrence of caries. Controlled administration of B. lactis BB-12 significantly reduced the incidence of respiratory infections during the first eight months of life in a Finnish population with breastfed infants. To conclude, administration of B. lactis BB-12 in early childhood is safe with regard to the future dental health of the child. In addition, B. lactis BB-12 may add to the protection against respiratory infections provided by human breast milk in infancy.

Maternal age and adverse perinatal outcomes in a birth cohort (BRISA) from a Northeastern Brazilian city

PURPOSE:To verify the existence of associations between different maternal ages and the perinatal outcomes of preterm birth and intrauterine growth restriction in the city of São Luís, Maranhão, Northeastern Brazil.METHODS:A cross-sectional study using a sample of 5,063 hospital births was conducted in São Luís, from January to December 2010. The participants comprise the birth cohort for the study "Etiological factors of preterm birth and consequences of perinatal factors for infant health: birth cohorts from two Brazilian cities" (BRISA). Frequencies and 95% confidence intervals were used to describe the results. Multiple logistic regression models were applied to assess the adjusted odds ratio (OR) of maternal age associated with the following outcomes: preterm birth and intrauterine growth restriction.RESULTS:The percentage of early teenage pregnancy (12–15 years old) was 2.2%, and of late (16–19 years old) was 16.4%, while pregnancy at an advanced maternal age (>35 years) was 5.9%. Multivariate analyses showed a statistically significant increase in preterm births among females aged 12–15 years old (OR=1.6; p=0.04) compared with those aged 20–35 years. There was also a higher rate in preterm births among females aged 16–19 years old (OR=1.3; p=0.01). Among those with advanced maternal age (>35 years old), the increase in the prevalence of preterm birth had only borderline statistical significance (OR=1.4; p=0.05). There was no statistically significant association between maternal age and increased prevalence of intrauterine growth restriction.

Criteria for prediction of metastatic axillary lymph nodes in early-stage breast cancer

PURPOSE: To estimate the likelihood of axillary lymph node involvement for patients with early-stage breast cancer, based on a variety of clinical and pathological factors. METHODS: A retrospective analysis was done in hospital databases from 1999 to 2007. Two hundred thirty-nine patients were diagnosed with early-stage breast cancer. Predictive factors, such as patient age, tumor size, lymphovascular invasion, histological grade and immunohistochemical subtype were analyzed to identify variables that may be associated with axillary lymph node metastasis. RESULTS: Patients with tumors that are negative for estrogen receptor, progesterone receptor, and HER2 had approximately a 90% lower chance of developing lymph node metastasis than those with luminal A tumors (e.g., ER+ and/or PR+ and HER2-) - Odds Ratio: 0.11; 95% confidence interval: 0.01-0.88; p=0.01. Furthermore, the risk for lymph node metastasis of luminal A tumors seemed to decrease as patient age increased, and it was directly correlated with tumor size. CONCLUSION: The molecular classification of early-stage breast cancer using immunohistochemistry may help predicting the probability of developing axillary lymph node metastasis. Further studies are needed to optimize predictions for nodal involvement, with the aim of aiding the decision-making process for breast cancer treatment.

Lithostratigraphy and age of pre-Late Weichselian sediments in the Suupohja area, western Finland

Different types of laterally extensive sand- and gravel-dominated deposits, up to several tens of metres thick, were investigated in the Suupohja area of western Finland. The studied sediments were deposited in glacial, ice-marginal, glaciofluvial, sea or lake, littoral and terrestrial environments during several glacial-non-glacial cycles. Seventeen pre-Late Weichselian and three Late Weichselian/Holocene sedimentary units were identified. These were divided into ten formally and two informally defined formations that were together termed the Suupohja Group. Every unit are nevertheless not detectable throughout the study area. The informally defined “Karhukangas lower deposits” represent the lowest units in the Suupohja Group. The Karhukangas lower deposits with 5 till units, 3 glaciolacustrine/-marine units and 2 sand units, were interpreted as having been deposited during possibly four glacial-non-glacial cycles before the Late Pleistocene Subepoch (MIS 6 or earlier). The Kankalo Sand above the Karhukangas lower deposits comprises glaciofluvial and aeolian sands of Late Saalian, Eemian or Early Weichselian origin (MIS 6–MIS 5c). The Kariluoma Till above the Kankalo Sand was possibly deposited during the Late Saalian glacial advance, although an Early Weichselian origin is also possible. The Harrinkangas Formation, with glaciofluvial and quiet-water sediments, is interpreted as having been deposited during the Late Saalian and Eemian Stages (MIS 6–MIS 5e). The uppermost units in the deposits studied, the Kodesjärvi Formation (shore deposit), Isojoki Sand (aeolian), Rävåsen Formation (glaciofluvial), Vanhakylä Formation (shore line deposit), Dagsmark Till and Kauhajoki Till, were deposited during the Weichselian Stage (MIS 5d–MIS 2). In addition, Early Holocene (MIS 1) eskers without till cover were informally termed the “Holocene esker deposits”. The Lumikangas Formation represents gravelly shore deposits formed in the Holocene Epoch, when these areas last emerged from the sea. The first Weichselian ice expansion possibly reached the western part of Suupohja in the Early Weichselian Substage (MIS 5d?), but it did not expand further to the east. The second Weichselian glaciation of relatively short duration occupied the southern part of Finland in the later part of Middle Weichselian (MIS 3). Thus, the southern half of the country remained ice-free for the majority (~65–75%) of the Weichselian Stage. Instead, both humid temperate and periglacial conditions alternated. In the initial part of Middle Weichselian, this area was partly submerged, which indicates eastward expansion of the Scandinavian ice sheet(s), depressing the lithosphere. The exceptionally thick sediment cover, multiple lithofacies, relict landscape and preserved preglacially weathered bedrock are evidence of weak glacial erosion in the Suupohja area during the latest as well as earlier glaciations, making this area one of the key areas in Quaternary research.

Response threshold to aversive stimuli in stimulated early protein-malnourished rats

Two animal models of pain were used to study the effects of short-term protein malnutrition and environmental stimulation on the response threshold to aversive stimuli. Eighty male Wistar rats were used. Half of the pups were submitted to malnutrition by feeding their mothers a 6% protein diet from 0 to 21 days of age while the mothers of the other half (controls) were well nourished, receiving 16% protein. From 22 to 70 days all rats were fed commercial lab chow. Half of the animals in the malnourished and control groups were maintained under stimulating conditions, including a 3-min daily handling from 0 to 70 days and an enriched living cage after weaning. The other half was reared in a standard living cage. At 70 days, independent groups of rats were exposed to the shock threshold or to the tail-flick test. The results showed lower body and brain weights in malnourished rats when compared with controls at weaning and testing. In the shock threshold test the malnourished animals were more sensitive to electric shock and environmental stimulation increased the shock threshold. No differences due to diet or environmental stimulation were found in the tail-flick procedure. These results demonstrate that protein malnutrition imposed only during the lactation period is efficient in inducing hyperreactivity to electric shock and that environmental stimulation attenuates the differences in shock threshold produced by protein malnutrition

Spontaneous Focusing on Numerosity in the Development of Early Mathematical Skills

The aim of the present set of longitudinal studies was to explore 3-7-year-old children.s Spontaneous FOcusing on Numerosity (SFON) and its relation to early mathematical development. The specific goals were to capture in method and theory the distinct process by which children focus on numerosity as a part of their activities involving exact number recognition, and individual differences in this process that may be informative in the development of more complex number skills. Over the course of conducting the five studies, fifteen novel tasks were progressively developed for the SFON assessments. In the tasks, confounding effects of insufficient number recognition, verbal comprehension, other procedural skills as well as working memory capacity were aimed to be controlled. Furthermore, how children.s individual differences in SFON are related to their development of number sequence, subitizing-based enumeration, object counting and basic arithmetic skills was explored. The effect of social interaction on SFON was tested. Study I captured the first phase of the 3-year longitudinal study with 39 children. It was investigated whether there were differences in 3-year-old children.s tendency to focus on numerosity, and whether these differences were related to the children.s development of cardinality recognition skills from the age of 3 to 4 years. It was found that the two groups of children formed on the basis of their amount of SFON tendency at the age of 3 years differed in their development of recognising and producing small numbers. The children whose SFON tendency was very predominant developed faster in cardinality related skills from the age of 3 to 4 years than the children whose SFON tendency was not as predominant. Thus, children.s development in cardinality recognition skills is related to their SFON tendency. Studies II and III were conducted to investigate, firstly, children.s individual differences in SFON, and, secondly, whether children.s SFON is related to their counting development. Altogether nine tasks were designed for the assessments of spontaneous and guided focusing on numerosity. The longitudinal data of 39 children in Study II from the age of 3.5 to 6 years showed individual differences in SFON at the ages of 4, 5 and 6 years, as well as stability in children.s SFON across tasks used at different ages. The counting skills were assessed at the ages of 3.5, 5 and 6 years. Path analyses indicated a reciprocal tendency in the relationship between SFON and counting development. In Study III, these results on the individual differences in SFON tendency, the stability of SFON across different tasks and the relationship of SFON and mathematical skills were confirmed by a larger-scale cross-sectional study of 183 on average 6.5-year-old children (range 6;0-7;0 years). The significant amount of unique variance that SFON accounted for number sequence elaboration, object counting and basic arithmetic skills stayed statistically significant (partial correlations varying from .27 to .37) when the effects of non-verbal IQ and verbal comprehension were controlled. In addition, to confirm that the SFON tasks assess SFON tendency independently from enumeration skills, guided focusing tasks were used for children who had failed in SFON tasks. It was explored whether these children were able to proceed in similar tasks to SFON tasks once they were guided to focus on number. The results showed that these children.s poor performance in the SFON tasks was not caused by their deficiency in executing the tasks but on lacking focusing on numerosity. The longitudinal Study IV of 39 children aimed at increasing the knowledge of associations between children.s long-term SFON tendency, subitizing-based enumeration and verbal counting skills. Children were tested twice at the age of 4-5 years on their SFON, and once at the age of 5 on their subitizing-based enumeration, number sequence production, as well as on their skills for counting of objects. Results showed considerable stability in SFON tendency measured at different ages, and that there is a positive direct association between SFON and number sequence production. The association between SFON and object counting skills was significantly mediated by subitizing-based enumeration. These results indicate that the associations between the child.s SFON and sub-skills of verbal counting may differ on the basis of how significant a role understanding the cardinal meanings of number words plays in learning these skills. The specific goal of Study V was to investigate whether it is possible to enhance 3-year old children.s SFON tendency, and thus start children.s deliberate practice in early mathematical skills. Participants were 3-year-old children in Finnish day care. The SFON scores and cardinality-related skills of the experimental group of 17 children were compared to the corresponding results of the 17 children in the control group. The results show an experimental effect on SFON tendency and subsequent development in cardinality-related skills during the 6-month period from pretest to delayed posttest in the children with some initial SFON tendency in the experimental group. Social interaction has an effect on children.s SFON tendency. The results of the five studies assert that within a child.s existing mathematical competence, it is possible to distinguish a separate process, which refers to the child.s tendency to spontaneously focus on numerosity. Moreover, there are significant individual differences in children.s SFON at the age of 3-7 years. Moderate stability was found in this tendency across different tasks assessed both at the same and at different ages. Furthermore, SFON tendency is related to the development of early mathematical skills. Educational implications of the findings emphasise, first, the importance of regarding focusing on numerosity as a separate, essential process in the assessments of young children.s mathematical skills. Second, the substantial individual differences in SFON tendency during the childhood years suggest that uncovering and modeling this kind of mathematically meaningful perceiving of the surroundings and tasks could be an efficient tool for promoting young children.s mathematical development, and thus prevent later failures in learning mathematical skills. It is proposed to consider focusing on numerosity as one potential sub-process of activities involving exact number recognition in future studies.

Early prediction of poor outcome in patients with acute asthma in the emergency room

Early identification of patients who need hospitalization or patients who should be discharged would be helpful for the management of acute asthma in the emergency room. The objective of the present study was to examine the clinical and pulmonary functional measures used during the first hour of assessment of acute asthma in the emergency room in order to predict the outcome. We evaluated 88 patients. The inclusion criteria were age between 12 and 55 years, forced expiratory volume in the first second below 50% of predicted value, and no history of chronic disease or pregnancy. After baseline evaluation, all patients were treated with 2.5 mg albuterol delivered by nebulization every 20 min in the first hour and 60 mg of intravenous methylprednisolone. Patients were reevaluated after 60 min of treatment. Sixty-five patients (73.9%) were successfully treated and discharged from the emergency room (good responders), and 23 (26.1%) were hospitalized or were treated and discharged with relapse within 10 days (poor responders). A predictive index was developed: peak expiratory flow rates after 1 h <=0% of predicted values and accessory muscle use after 1 h. The index ranged from 0 to 2. An index of 1 or higher presented a sensitivity of 74.0, a specificity of 69.0, a positive predictive value of 46.0, and a negative predictive value of 88.0. It was possible to predict outcome in the first hour of management of acute asthma in the emergency room when the index score was 0 or 2.

Combined effect of short stature and socioeconomic status on body mass index and weight gain during reproductive age in Brazilian women

Short stature, a marker for undernutrition early in life, has been associated with obesity in Brazilian women, but not in men. We tested the hypothesis that weight gain during the reproductive years could explain this gender difference. A national two-stage household survey of mothers with one or more children under five years of age was conducted in Brazil in 1996. The subjects were women aged 20 to 45 years (N = 2297), with last delivery seven months or more prior to the interview. The regions of the country were divided into rural, North/Northeast (urban underdeveloped) and South/Southeast/Midwest (urban developed). The dependent variables were current body mass index (BMI) measured, BMI prior to childbearing (reported), and BMI change. Socioeconomic variables included mother's years of education and family purchasing power score. A secondary analysis was restricted to primiparous women. The prevalence of current overweight and overweight prior to childbearing (BMI > or = 25 kg/m²) was higher among shorter women (<1.50 m) compared to normal stature women only in the urban developed region (P < 0.05). After adjustment for socioeconomic variables, age, parity, BMI prior to childbearing, and age at first birth, current BMI was 2.39 units higher (P = 0.008) for short stature women living in the urban developed area compared with short stature women living in the urban underdeveloped area. For both multiparous and primiparous women, BMI gain compared to the value prior to childbearing was significantly higher among short stature women living in the urban developed region (P <= 0.04). These results provide clear evidence that short stature was associated with a higher BMI and with an increased risk of weight gain/retention with pregnancy in the developed areas of Brazil, but not in the underdeveloped ones.

Infrared coagulation versus rubber band ligation in early stage hemorrhoids

The ideal therapy for early stages of hemorrhoids is always debated. Some are more effective but are more painful, others are less painful but their efficacy is also lower. Thus, comfort or efficacy is a major concern. In the present randomized study, a comparison is made between infrared coagulation and rubber band ligation in terms of effectiveness and discomfort. One hundred patients with second degree bleeding piles were randomized prospectively to either rubber band ligation (N = 54) or infrared coagulation (N = 46). Parameters measured included postoperative discomfort and pain, time to return to work, relief in incidence of bleeding, and recurrence rate. The mean age was 38 years (range 19-68 years). The mean duration of disease was 17.5 months (range 12 to 34 months). The number of male patients was double that of females. Postoperative pain during the first week was more intense in the band ligation group (2-5 vs 0-3 on a visual analogue scale). Post-defecation pain was more intense with band ligation and so was rectal tenesmus (P = 0.0059). The patients in the infrared coagulation group resumed their duties earlier (2 vs 4 days, P = 0.03), but also had a higher recurrence or failure rate (P = 0.03). Thus, we conclude that band ligation, although more effective in controlling symptoms and obliterating hemorrhoids, is associated with more pain and discomfort to the patient. As infrared coagulation can be conveniently repeated in case of recurrence, it could be considered to be a suitable alternative office procedure for the treatment of early stage hemorrhoids.

Age-related changes in radiation-induced micronuclei among healthy adults

The aim of the present study was to establish the extent of in vitro radioresponse of lymphocytes among 62 healthy adults of both genders and to estimate the distribution of baseline micronuclei and radiosensitivity among individuals of the study population using the cytochalasin block micronucleus test. A younger study group consisted of 10 males (mean age, 22.4 years; range, 21-27) and 12 females (mean age, 24.8 years; range, 20-29), whereas an older study group consisted of 18 males (mean age, 35.1 years; range, 30-44) and 22 females (mean age, 38.5 years; range, 30-48). For evaluation of radiosensitivity blood samples were irradiated in vitro using 60Co g-ray source. The radiation dose employed was 2 Gy, the dose rate 0.45 Gy/min. The study revealed a significant gender effect on baseline micronuclei favoring females (Z = 3.25, P < 0.001), while yields of radiation-induced micronuclei did not differ significantly (Z = 0.56, P < 0.56) between genders. The distribution of baseline micronuclei among the individuals tested followed Poisson distribution in both study groups and in both genders, whereas the distribution of radiosensitivity among individuals of the older study group did not fulfill Poisson expectations (Kolmogorov-Smirnof test, P < 0.01). In contrast to a nonsignificant difference in radiosensitivity between males and females of the same age group (Z = 1.97, P < 0.56), a statistically significant difference in radiosensitivity between younger and older group for both genders was found (Z = 3.03, P < 0.03). Since the individuals tested were healthy, the observed variability in radiation response is considered to be an early effect of ageing.

Early Life Intestinal Microbiota in Health and in Atopic Eczema

Decrease in microbial contacts in affluent societies is considered to lie behind the rise in allergic and other chronic inflammatory diseases during the last decades. Indeed, deviations in the intestinal microbiota composition and diversity have been associated with several diseases, such as atopic eczema. However, there is no consensus yet on what would constitute a beneficial or harmful microbiota. The aim of this thesis was to study the microbiota development in healthy infants and to characterize intestinal microbiota signatures associated with disease status and severity in infants with atopic eczema. The methodological aim was to compare and optimize methods for DNA extraction from fecal samples to be used in high-throughput microbiota analyses. It was confirmed that the most critical step in successful microbial DNA extraction from fecal samples is the mechanical cell lysis procedure. Based on this finding, an efficient semi-automated extraction process was developed that can be scaled for use in high-throughput platforms such as phylogenetic microarray used in this series of studies. By analyzing a longitudinal motherchild cohort for 3 years it was observed that the microbiota development is a gradual process, where some bacterial groups reach the degree of adult-type pattern earlier than others. During the breast-feeding period, the microbiota appeared to be relatively simple, while major diversification was found to start during the weaning process. By the age of 3 years, the child’s microbiota composition started to resemble that of an adult, but the bacterial diversity has still not reached the full diversity, indicating that the microbiota maturation extends beyond this age. In addition, at three years of age, the child’s microbiota was more similar to mother’s microbiota than to microbiota of nonrelated women.In infants with atopic eczema, a high total microbiota diversity and abundance of butyrate-producing bacteria was found to correlate with mild symptoms at 6 months. At 18 months, infants with mild eczema had significantly higher microbiota diversity and aberrant microbiota composition when compared to healthy controls at the same age. In conclusion, the comprehensive phylogenetic microarray analysis of early life microbiota shows the synergetic effect of vertical transmission and shared environment on the intestinal microbiota development. By the age of three years, the compositional development of intestinal microbiota is close to adult level, but the microbiota diversification continues beyond this age. In addition, specific microbiota signatures are associated with the existence and severity of atopic eczema and intestinal microbiota seems to have a role in alleviating the symptoms of this disease.