Noise sensitivity medical, psychological and genetic aspects

Noise can be defined as unwanted sound. It may adversely affect the health and well-being of individuals. Noise sensitivity is a personality trait covering attitudes towards noise in general and a predictor of noise annoyance. Noise sensitive individuals are more affected by noise than less sensitive individuals. The determinants and characteristics related to noise sensitivity are rather poorly known. The risk of health effects caused by noise can be hypothesized to be higher for noise sensitive individuals compared to those who are not noise sensitive. A cardiovascular disease may be an example of outcomes. The general aim of the present study was to investigate the association of noise sensitivity with specific somatic and psychological factors, including the genetic component of noise sensitivity, and the association of noise sensitivity with mortality. The study was based on the Finnish Twin Cohort of same-sex twin pairs born before 1958. In 1988 a questionnaire was sent to twin pairs discordant for hypertension. 1495 individuals (688 men, 807 women) aged 31 88 years replied, including 573 twin pairs. 218 of the subjects lived in the Helsinki Metropolitan Area. Self-reported noise sensitivity, lifetime noise exposure and hypertension were obtained from the questionnaire study in 1988 and other somatic and psychological factors from the questionnaire study in 1981 for the same individuals. In addition, noise map information (1988 1992) from the Helsinki Metropolitan Area and mortality follow-up 1989 2003 were used. To evaluate the stability and validity of noise sensitivity, a new questionnaire was sent in 2002 to a sample of the subjects who had replied to the 1988 questionnaire. Of all subjects who had answered the question on noise sensitivity, 38 % were noise sensitive. Noise sensitivity was independent of noise exposure levels indicated in noise maps. Subjects with high noise sensitivity reported more transportation noise exposure than subjects with low noise sensitivity. Noise sensitive subjects reported transportation noise exposure outside the environmental noise map areas almost twice as often as non-sensitive subjects. Noise sensitivity was associated with hypertension, emphysema, use of psychotropic drugs, smoking, stress and hostility, even when lifetime noise exposure was adjusted for. Monozygotic twin pairs were more similar with regards noise sensitivity than dizygotic twin pairs, and quantitative genetic modelling indicated significant familiality. The best fitting genetic model provided an estimate of heritability of 36 %. Follow-up of subjects in the case-control study showed that cardiovascular mortality was significantly increased among noise sensitive women, but not among men. For coronary heart mortality the interaction of noise sensitivity and lifetime noise exposure was statistically significant in women. In conclusion, noise sensitivity has both somatic and psychological components. It does aggregate in families and probably has a genetic component. Noise sensitivity may be a risk factor for cardiovascular mortality in women.

Measurements of adequacy of anesthesia and level of consciousness during surgery and intensive care

The adequacy of anesthesia has been studied since the introduction of balanced general anesthesia. Commercial monitors based on electroencephalographic (EEG) signal analysis have been available for monitoring the hypnotic component of anesthesia from the beginning of the 1990s. Monitors measuring the depth of anesthesia assess the cortical function of the brain, and have gained acceptance during surgical anesthesia with most of the anesthetic agents used. However, due to frequent artifacts, they are considered unsuitable for monitoring consciousness in intensive care patients. The assessment of analgesia is one of the cornerstones of general anesthesia. Prolonged surgical stress may lead to increased morbidity and delayed postoperative recovery. However, no validated monitoring method is currently available for evaluating analgesia during general anesthesia. Awareness during anesthesia is caused by an inadequate level of hypnosis. This rare but severe complication of general anesthesia may lead to marked emotional stress and possibly posttraumatic stress disorder. In the present series of studies, the incidence of awareness and recall during outpatient anesthesia was evaluated and compared with that of in inpatient anesthesia. A total of 1500 outpatients and 2343 inpatients underwent a structured interview. Clear intraoperative recollections were rare the incidence being 0.07% in outpatients and 0.13% in inpatients. No significant differences emerged between outpatients and inpatients. However, significantly smaller doses of sevoflurane were administered to outpatients with awareness than those without recollections (p<0.05). EEG artifacts in 16 brain-dead organ donors were evaluated during organ harvest surgery in a prospective, open, nonselective study. The source of the frontotemporal biosignals in brain-dead subjects was studied, and the resistance of bispectral index (BIS) and Entropy to the signal artifacts was compared. The hypothesis was that in brain-dead subjects, most of the biosignals recorded from the forehead would consist of artifacts. The original EEG was recorded and State Entropy (SE), Response Entropy (RE), and BIS were calculated and monitored during solid organ harvest. SE differed from zero (inactive EEG) in 28%, RE in 29%, and BIS in 68% of the total recording time (p<0.0001 for all). The median values during the operation were SE 0.0, RE 0.0, and BIS 3.0. In four of the 16 organ donors, EEG was not inactive, and unphysiologically distributed, nonreactive rhythmic theta activity was present in the original EEG signal. After the results from subjects with persistent residual EEG activity were excluded, SE, RE, and BIS differed from zero in 17%, 18%, and 62% of the recorded time, respectively (p<0.0001 for all). Due to various artifacts, the highest readings in all indices were recorded without neuromuscular blockade. The main sources of artifacts were electrocauterization, electromyography (EMG), 50-Hz artifact, handling of the donor, ballistocardiography, and electrocardiography. In a prospective, randomized study of 26 patients, the ability of Surgical Stress Index (SSI) to differentiate patients with two clinically different analgesic levels during shoulder surgery was evaluated. SSI values were lower in patients with an interscalene brachial plexus block than in patients without an additional plexus block. In all patients, anesthesia was maintained with desflurane, the concentration of which was targeted to maintain SE at 50. Increased blood pressure or heart rate (HR), movement, and coughing were considered signs of intraoperative nociception and treated with alfentanil. Photoplethysmographic waveforms were collected from the contralateral arm to the operated side, and SSI was calculated offline. Two minutes after skin incision, SSI was not increased in the brachial plexus block group and was lower (38 ± 13) than in the control group (58 ± 13, p<0.005). Among the controls, one minute prior to alfentanil administration, SSI value was higher than during periods of adequate antinociception, 59 ± 11 vs. 39 ± 12 (p<0.01). The total cumulative need for alfentanil was higher in controls (2.7 ± 1.2 mg) than in the brachial plexus block group (1.6 ± 0.5 mg, p=0.008). Tetanic stimulation to the ulnar region of the hand increased SSI significantly only among patients with a brachial plexus block not covering the site of stimulation. Prognostic value of EEG-derived indices was evaluated and compared with Transcranial Doppler Ultrasonography (TCD), serum neuron-specific enolase (NSE) and S-100B after cardiac arrest. Thirty patients resuscitated from out-of-hospital arrest and treated with induced mild hypothermia for 24 h were included. Original EEG signal was recorded, and burst suppression ratio (BSR), RE, SE, and wavelet subband entropy (WSE) were calculated. Neurological outcome during the six-month period after arrest was assessed with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Twenty patients had a CPC of 1-2, one patient had a CPC of 3, and nine patients died (CPC 5). BSR, RE, and SE differed between good (CPC 1-2) and poor (CPC 3-5) outcome groups (p=0.011, p=0.011, p=0.008, respectively) during the first 24 h after arrest. WSE was borderline higher in the good outcome group between 24 and 48 h after arrest (p=0.050). All patients with status epilepticus died, and their WSE values were lower (p=0.022). S-100B was lower in the good outcome group upon arrival at the intensive care unit (p=0.010). After hypothermia treatment, NSE and S-100B values were lower (p=0.002 for both) in the good outcome group. The pulsatile index was also lower in the good outcome group (p=0.004). In conclusion, the incidence of awareness in outpatient anesthesia did not differ from that in inpatient anesthesia. Outpatients are not at increased risk for intraoperative awareness relative to inpatients undergoing general anesthesia. SE, RE, and BIS showed non-zero values that normally indicate cortical neuronal function, but were in these subjects mostly due to artifacts after clinical brain death diagnosis. Entropy was more resistant to artifacts than BIS. During general anesthesia and surgery, SSI values were lower in patients with interscalene brachial plexus block covering the sites of nociceptive stimuli. In detecting nociceptive stimuli, SSI performed better than HR, blood pressure, or RE. BSR, RE, and SE differed between the good and poor neurological outcome groups during the first 24 h after cardiac arrest, and they may be an aid in differentiating patients with good neurological outcomes from those with poor outcomes after out-of-hospital cardiac arrest.

The relationships between work stressors and organizational performance in long-term care for elderly residents

This study investigates the relationships between work stressors and organizational performance in terms of the quality of care provided by the long-term care facilities. Work stressors are first examined in relation to the unit's structural factors, resident characteristics, and to the unit specialization. The study is completed by an investigation into the associations of work stressors such as job demands or time pressure, role ambiguity, resident-related stress, and procedural injustice to organizational performance. Also the moderating effect of job control in the job demands organizational performance relationship is examined. The study was carried out in the National Research and Development Centre for Welfare and Health (STAKES). Survey data were drawn from 1194 nursing employees in 107 residential-home and health-center inpatient units in 1999 and from 977 employees in 91 units in 2002. Information on the unit resident characteristics and the quality of care was provided by the Resident Assessment Instrument (RAI). The results showed that large unit size or lower staffing levels were not consistently related to work stressors, whereas the impairments in residents' physical functioning in particular initiated stressful working conditions for employees. However, unit specialization into dementia and psychiatric residents was found to buffer the effects that the resident characteristics had on employee appraisals of work stressors, in that a high proportion of behavioral problems was related to less time pressure and role conflicts for employees in specialized units. Unit specialization was also related to improved team climates and the organizational commitment of employees. Work stressors associated with problems in care quality. Time pressure explained most of the differences between units in how the employees perceived the quality of physical and psychosocial care they provide for the residents. A high level of job demands in the unit was also found to be related to some increases in all clinical quality problems. High job control buffered the effects of job demands on the quality of care in terms of the use of restraints on elderly residents. Physical restraint and especially antipsychotic drug use were less prevalent in units that combined both high job demands and high control for employees. In contrast, in high strain units where heavy job demands coincided with a lack of control for employees, quality was poor in terms of the frequent use of physical restraints. In addition, procedural injustice was related to the frequent use of antianxiety of hypnotic drugs for elderly residents. The results suggest that both job control and procedural justice may have improved employees' abilities to cope when caring for the elderly residents, resulting in better organizational performance.

Developmental origins of physiological stress reactivity

The model of developmental origins of health and disease proposes that organisms during fetal period utilize cues that enable their adaptation in the postnatal environment they are likely to live, having short-term advantages when trying to survive in environment but simultaneously in the long run have costs for health. A large body of epidemiological research has found that low birth weight, a marker of intrauterine conditions, is associated with cardiovascular (CV) disease. Since the reported associations of birth weight with normal variation in the resting blood pressure (BP), a major predictor of CV disease risk, have been modest, a key candidate mediating the link has been CV and hypothalamus-pituitary-adrenal axes (HPAA) reactivity to stress. In addition, not only weight at birth but also gestational age and early postnatal growth may have independent associations to stress reactivity. The aim of this thesis was to investigate whether pre- and postnatal growth and gestational age are associated with CV and HPAA activity before, during and after stress in childhood and in late adulthood. Altogether 287 men and women aged 60-70 and 299 boys and girls aged 7-9 underwent Trier Social Stress Test. Several indices of HPAA and CV were measured and birth size and gestational age were obtained from birth records. Results showed that low birth weight was associated with low HPAA activity during psychosocial stress, and rapid gain in BMI during years 7-11 was related to heightened stress reactivity to psychosocial stress. Size at birth in children and gestational age and early postnatal (0-2 years) gain in height in adults were associated with CV stress responses; however, in a sex-specific manner. Given that CV stress responses and HPAA activity are markers of CV disease vulnerability, our results may partly explain the associations between early environment and later CV disease.

Acquisition of focus by normal hearing and Cochlear implanted children

Two experiments investigated the perception of compound vs. phrasal stress and narrow focus in normally hearing children and children with Cochlear Implants (CI). Additionally, we investigated whether musical experience would predict children’s performance in these tasks. The results showed no difference between CI and normal-hearing (NH) children in either experiment. However, whereas we found no clear effect of age in the children’s stress detection, there was a clear age related trajectory in the ability to recognise (narrow) focus. Moreover, this trend was similar to what has been found previously for English children. Importantly, prior music experience was significantly linked to CI children’s perception of focus.

The connection between on-farm assessed welfare (A-index) and production parameters of the sows

Tämän tutkimuksen tavoitteena oli selvittää tilalla määritetyn hyvinvoinnin yhteyttä emakoiden tuotantotuloksiin. Hyvinvointia arvioitiin suomalaisen hyvinvointi-indeksin, A-indeksi, avulla. Tuotantotuloksina käytettiin kahta erilaista tuotosaineistoa, jotka molemmat pohjautuivat kansalliseen tuotosseuranta aineistoon. Hyvinvointimääritykset tehtiin 30 porsastuotantosikalassa maaliskuun 2007 aikana. A-indeksi koostuu kuudesta kategoriasta ’liikkumismahdollisuudet’, ’alustan ominaisuudet’, ’sosiaaliset kontaktit’, ’valo, ilma ja melu’, ’ruokinta ja veden saanti’ sekä ’eläinten terveys ja hoidon taso’. Jokaisessa kategoriassa on 3-10 pääosin ympäristöperäistä muuttujaa, jotka vaihtelevat osastoittain. Maksimipistemäärä osastolle on 100. Hyvinvointimittaukset tehtiin porsitus-, tiineytys- ja joutilasosastoilla. Erillisten tiineytysosastojen pienen lukumäärän takia (n=7) tilakohtaiset tiineytys- ja joutilasosastopisteet yhdistettiin ja keskiarvoja käytettiin analyyseissä. Yhteyksiä tuotokseen tutkittiin kahden eri aineiston avulla 1) Tilaraportti aineisto (n=29) muodostuu muokkaamattomista tila- ja tuotostuloksista tilavierailua edeltävän vuoden ajalta, 2) POTSIaineisto (n=30) muodostuu POTSI-ohjelmalla (MTT) muokatusta tuotantoaineistosta, joka sisältää managementtiryhmän (tila, vuosi, vuodenaika) vaikutuksen ensikoiden ja emakoiden pahnuekohtaiseen tuotokseen. Yhteyksiä analysointiin korrelaatio- ja regressioanalyysien avulla. Vaikka osallistuminen tutkimukseen oli vapaaehtoista, molempien tuotantoaineistojen perusteella tutkimustilat edustavat keskituottoista suomalaista sikatilaa. A-indeksin kokonaispisteet vaihtelivat välillä 37,5–64,0 porsitusosastolla ja 39,5–83,5 joutilasosastolla. Tilaraporttiaineistoa käytettäessä paremmat pisteet porsitusosaston ’eläinten terveys ja hoidon taso’ -kategoriasta lyhensivät eläinten lisääntymissykliä, lisäsivät syntyvien pahnueiden ja porsaiden määrää sekä alensivat kuolleena syntyneiden lukumäärää. Regressiomallin mukaan ’eläinten terveys ja hoidon taso’ -kategoria selitti syntyvien porsaiden lukumäärän, porsimisvälin pituuden sekä keskiporsimiskerran vaihtelua. Paremmat pisteet joutilasosaston ’liikkumismahdollisuudet’ kategoriasta alensivat syntyneiden pahnueiden sekä syntyneiden että vieroitettujen porsaiden lukumäärää. Regressiomallin mukaan ensikkopahnueiden osuus ja ”liikkumismahdollisuudet” kategorian pisteet selittivät vieroitettujen porsaiden lukumäärän vaihtelua. POTSI-aineiston yhteydessä kuolleena syntyneiden porsaiden lukumäärän aleneminen oli ensikoilla yhteydessä parempiin porsitusosaston ’sosiaalisiin kontakteihin’ ja emakoilla puolestaan joutilasosaston parempiin ’eläinten terveys ja hoidon taso’ pisteisiin. Kahden eri tuotantoaineiston avulla saadut tulokset erosivat toisistaan. Seuraavissa tutkimuksissa onkin suositeltavampaa käyttää Tilaraporttiaineistoja, joissa tuotokset ilmoitetaan vuosikohtaisina. Tämän tutkimuksen perusteella hyvinvoinnilla ja tuotoksella on yhteyksiä, joilla on myös merkittävää taloudellista vaikutusta. Erityisesti hyvä eläinten hoito ja eläinten terveys lisäävät tuotettujen porsaiden määrää ja lyhentävät lisääntymiskiertoa. Erityishuomiota tulee kiinnittää vapaana olevien joutilaiden emakoiden sosiaaliseen stressiin ja rehunsaannin varmistamiseen kaikille yksilöille.

University Students' Approaches to Learning, Self-Regulation, and Cognitive and Attributional Strategies : Connections with Well-Being and Academic Success

This dissertation empirically explores the relations among three theoretical perspectives: university students approaches to learning, self-regulated learning, as well as cognitive and attributional strategies. The relations were quantitatively studied from both variable- and person-centered perspectives. In addition, the meaning that students gave to their disciplinary choices was examined. The general research questions of the study were: 1) What kinds of relationships exist among approaches to learning, regulation of learning, and cognitive and attributional strategies? What kinds of cognitive-motivational profiles can be identified among university students, and how are such profiles related to study success and well-being? 3) How do university students explain their disciplinary choices? Four empirical studies addressed these questions. Studies I, II, and III were quantitative, applying self-report questionnaires, and Study IV was qualitative in nature. Study I explored relations among cognitive strategies, approaches to learning, regulation of learning, and study success by using correlations and a K-means cluster analysis. The participants were 366 students from various faculties at different phases of their studies. The results showed that all the measured constructs were logically related to each other in both variable- and person-centered approaches. Study II further examined what kinds of cognitive-motivational profiles could be identified among first-year university students (n=436) in arts, law, and agriculture and forestry. Differences in terms of study success, exhaustion, and stress among students with differing profiles were also looked at. By using a latent class cluster analysis (LCCA), three groups of students were identified: non-academic (34%), self-directed (35%), and helpless students (31%). Helpless students reported the highest levels of stress and exhaustion. Self-directed students received the highest grades. In Study III, cognitive-motivational profiles were identified among novice teacher students (n=213) using LCCA. Well-being, epistemological beliefs, and study success were looked at in relation to the profiles. Three groups of students were found: non-regulating (50%), self-directed (35%), and non-reflective (22%). Self-directed students again received the best grades. Non-regulating students reported the highest levels of stress and exhaustion, the lowest level of interest, and showed the strongest preference for certain and practical knowledge. Study IV, which was qualitative in nature, explored how first-year students (n = 536 ) in three fields of studies, arts, law, and veterinary medicine explained their disciplinary choices. Content analyses showed that interest appeared to be a common concept in students description of their choices across the three faculties. However, the objects of interest of the freshmen appeared rather unspecified. Veterinary medicine and law students most often referred to future work or a profession, whereas only one-fifth of the arts students did so. The dissertation showed that combining different theoretical perspectives and methodologies enabled us to build a rich picture of university students cognitive and motivational predispositions towards studying and learning. Further, cognitive-emotional aspects played a significant role in studying, not only in relation to study success, but also in terms of well-being. Keywords: approaches to learning, self-regulation, cognitive and attributional strategies, university students

Molecular mechanisms of hypertension-induced heart failure : Experimental studies with special emphasis on local renin-angiotensin system, cardiac metabolism and levosimendan

Hypertension is a major risk factor for stroke, ischaemic heart disease, and the development of heart failure. Hypertension-induced heart failure is usually preceded by the development of left ventricular hypertrophy (LVH), which represents an adaptive and compensatory response to the increased cardiac workload. Biomechanical stress and neurohumoral activation are the most important triggers of pathologic hypertrophy and the transition of cardiac hypertrophy to heart failure. Non-clinical and clinical studies have also revealed derangements of energy metabolism in hypertensive heart failure. The goal of this study was to investigate in experimental models the molecular mechanisms and signalling pathways involved in hypertension-induced heart failure with special emphasis on local renin-angiotensin-aldosterone system (RAAS), cardiac metabolism, and calcium sensitizers, a novel class of inotropic agents used currently in the treatment of acute decompensated heart failure. Two different animal models of hypertensive heart failure were used in the present study, i.e. hypertensive and salt-sensitive Dahl/Rapp rats on a high salt diet (a salt-sensitive model of hypertensive heart failure) and double transgenic rats (dTGR) harboring human renin and human angiotensinogen genes (a transgenic model of hypertensive heart failure with increased local RAAS activity). The influence of angiotensin II (Ang II) on cardiac substrate utilization and cardiac metabolomic profile was investigated by using gas chromatography coupled to time-of-flight mass spectrometry to detect 247 intermediary metabolites. It was found that Ang II could alter cardiac metabolomics both in normotensive and hypertensive rats in an Ang II receptor type 1 (AT1)-dependent manner. A distinct substrate use from fatty acid oxidation towards glycolysis was found in dTGR. Altered cardiac substrate utilization in dTGR was associated with mitochondrial dysfunction. Cardiac expression of the redox-sensitive metabolic sensor sirtuin1 (SIRT1) was increased in dTGR. Resveratrol supplementation prevented cardiovascular mortality and ameliorated Ang II-induced cardiac remodeling in dTGR via blood pressure-dependent pathways and mechanisms linked to increased mitochondrial biogenesis. Resveratrol dose-dependently increased SIRT1 activity in vitro. Oral levosimendan treatment was also found to improve survival and systolic function in dTGR via blood pressure-independent mechanisms, and ameliorate Ang II-induced coronary and cardiomyocyte damage. Finally, using Dahl/Rapp rats it was demonstrated that oral levosimendan as well as the AT1 receptor antagonist valsartan improved survival and prevented cardiac remodeling. The beneficial effects of levosimendan were associated with improved diastolic function without significantly improved systolic changes. These positive effects were potentiated when the drug combination was administered. In conclusion, the present study points to an important role for local RAAS in the pathophysiology of hypertension-induced heart failure as well as its involvement as a regulator of cardiac substrate utilization and mitochondrial function. Our findings suggest a therapeutic role for natural polyphenol resveratrol and calcium sensitizer, levosimendan, and the novel drug combination of valsartan and levosimendan, in prevention of hypertension-induced heart failure. The present study also provides a better understanding of the pathophysiology of hypertension-induced heart failure, and may help identify potential targets for novel therapeutic interventions.

Diabetic cardiomyopathy and post-infarct ventricular remodelling : Effects of levosimendan in a rodent model of type II diabetes

Type 2 diabetes is a risk factor for the development of cardiovascular disease. Recently, the term diabetic cardiomyopathy has been proposed to describe the changes in the heart that occur in response to chronic hyperglycemia and insulin resistance. Ventricular remodelling in diabetic cardiomyopathy includes left ventricular hypertrophy, increased interstitial fibrosis, apoptosis and diastolic dysfunction. Mechanisms behind these changes are increased oxidative stress and renin-angiotensin system activation. The diabetic Goto-Kakizaki rat is a non-obese model of type 2 diabetes that exhibits defective insulin signalling. Recently two interconnected stress response pathways have been discovered that link insulin signalling, longevity, apoptosis and cardiomyocyte hypertrophy. The insulin-receptor PI3K/Ak pathway inhibits proapoptotic FOXO3a in response to insulin signalling and the nuclear Sirt1 deacetylase inhibits proapoptotic p53 and modulates FOXO3a in favour of survival and growth. --- Levosimendan is a calcium sensitizing agent used for the management of acute decompensated heart failure. Levosimendan acts as a positive inotrope by sensitizing cardiac troponin C to calcium and exerts vasodilation by opening mitochondrial and sarcolemmal ATP-sensitive potassium channels. Levosimendan has been described to have beneficial effects in ventricular remodelling after myocardial infarction. The aims of the study were to characterize whether diabetic cardiomyopathy associates with cardiac dysfunction, cardiomyocyte apoptosis, hypertrophy and fibrosis in spontaneously diabetic Goto-Kakizaki (GK) rats, which were used to model type 2 diabetes. Protein expression and activation of the Akt FOXO3a and Sirt1 p53 pathways were examined in the development of ventricular remodelling in GK rats with and without myocardial infarction (MI). The third and fourth studies examined the effects of levosimendan on ventricular remodelling and gene expression in post-MI GK rats. The results demonstrated that diabetic GK rats develop both modest hypertension and features similar to diabetic cardiomyopathy including cardiac dysfunction, LV hypertrophy and fibrosis and increased apoptotic signalling. MI induced a sustained increase in cardiomyocyte apoptosis in GK rats together with aggravated LV hypertrophy and fibrosis. The GK rat myocardium exhibited decreased Akt- FOXO3a phosphorylation and increased nuclear translocation of FOXO3a and overproduction of the Sirt1 protein. Treatment with levosimendan decreased cardiomyocyte apoptosis, senescence and LV hypertrophy and altered the gene expression profile in GK rat myocardium. The findings indicate that impaired cardioprotection via Akt FOXO3a and p38 MAPK is associated with increased apoptosis, whereas Sirt1 functions in counteracting apoptosis and the development of LV hypertrophy in the GK rat myocardium. Overall, levosimendan treatment protects against post-MI ventricular remodelling and alters the gene expression profile in the GK rat myocardium.

Non-small cell lung cancer : studies on pathogenesis, tumour targeting and treatment outcomes

Lung cancer accounts for more cancer-related deaths than any other cancer. In Finland, five-year survival ranges from 8% to 13%. The main risk factor for lung cancer is long-term cigarette smoking, but its carcinogenesis requires several other factors. The aim of the present study was to 1) evaluate post-operative quality of life, 2) compare clinical outcomes between minimally invasive and conventional open surgery, 3) evaluate the role of oxidative stress in the carcinogenesis of non-small lung cancer (NSCLC), and 4) to identify and characterise targeted agents for therapeutic and diagnostic use in surgery. For study I, pneumonectomy patients replied to 15D quality of life and baseline dyspnea questionnaires. Study III involved a prospective quality of life assessment using the 15D questionnaire after lobectomy or bi-lobectomy. Study IV was a retrospective comparison of clinical outcomes between 212 patients treated with open thoracotomy and 116 patients who underwent a minimally invasive technique. Study II measured parameters of oxidative metabolism (myeloperoxidase activity, glutathione content and NADPH oxidase activity) and DNA adducts. Study V employed the phage display method and identified a core motif for homing peptides. This method served in cell-binding, cell-localisation, and biodistribution studies. Following both pneumonectomy and lobectomy, NSCLC patients showed significantly decreased long-term quality of life. No significant correlation was noted between post-operative quality of life and pre-operative pulmonary function tests. Women suffered more from increased dyspnea after pneumonectomy which was absent after lobectomy or bi-lobectomy. Patients treated with video-assisted thoracoscopy showed significantly decreased morbidity and shorter periods of hospitalization than did open surgery patients. This improvement was achieved even though the VATS patients were older and suffered more comorbid conditions and poorer pulmonary function. No significant differences in survival were noted between these two groups. An increase in NADPH oxidase activity was noted in tumour samples of both adenocarcinoma and squamous cell carcinoma. This increase was independent from myeloperoxidase activity. Elevated glutathione content was noted in tumour tissue, especially in adenocarcinoma. After panning the clinical tumour samples with the phage display method, an amino acid sequence of ARRPKLD, the Thx, was chosen for further analysis. This method proved selective of tumour tissue in both in vitro and in vivo cell-binding assay, and biodistribution showed tumour accumulation. Because of the significantly reduced quality of life following pneumonectomy, other operative strategies should be implemented as an alternative (e.g. sleeve-lobectomy). To treat this disease, implementation of a minimally invasive surgical technique is safe, and the results showed decreased morbidity and a shorter period of hospitalisation than with thoracotomy. This technique may facilitate operative treatment of elderly patients with comorbid conditions who might otherwise be considered inoperable. Simultaneous exposure to oxidative stress and altered redox states indicates the important role of oxidative stress in the pathogenesis and malignant transformation of NSCLC. The studies showed with great specificity and with favourable biodistribution that Thx peptide is specific to NSCLC tumours. Thx thus shows promise in imaging, targeted therapy, and monitoring of treatment response.

Process of burnout: structure, antecedents, and consequences

The major changes that have been witnessed in today's workplaces are challenging the mental well-being of employed people. Stress and burnout are considered to be modern epidemics, and their importance to physical health and work ability has been acknowledged world-wide. The aim of the thesis was to study the concept of burnout as a process proceeding from its antecedents, through the development of the syndrome, and to its outcomes. Several work-related factors considered antecedents of burnout were studied in different occupational groups. The syndrome of burnout is seen as consisting of three dimensions - exhaustion, cynicism and lack of professional efficacy - and different alternatives for the sequential development of these dimensions were tested. Furthermore, several indicators of the severely detrimental health and work ability outcomes of burnout were investigated in a longitudinal study design. The research questions were as follows. 1) Is burnout, as measured with the Maslach Burnout Inventory - General Survey (MBI-GS), a three-dimensional construct and how invariant is the factorial structure across occupations (Finnish) and national samples (Finnish, Swedish and Dutch)? How persistent is exhaustion over time? 2) What is the sequential process of burnout? Is it similar across occupations? How do work stressors relate to the process? 3) How does burnout relate to severe health consequences as well as temporary and chronic work disability according to hospitalization periods, sick-leave episodes and receiving disability pensions? The data were collected between 1986 and 2005. The population of the study consisted of respondents to a company-wide questionnaire survey carried out in 1996-1997 (N=9705, response rate 63%). The participants comprised 6025 blue-collar workers and 3680 white-collar workers. The majority were men (N=7494) and the average age was 43.7 years. In addition, a sample from the population had responded to a questionnaire survey in 1988, which was combined with the 1996 data to form panel data on 713 respondents. The register-based data were collected between 1986 and 2005 from 1) the company's occupational health services' records for a sample of respondents from the 1996 questionnaire survey (sick-leave data), 2) hospitalization records from the Hospital discharge register, and 3) disability pension records from the Finnish Centre for Pensions. These data were combined person by person with the 1996 questionnaire survey data with the help of personal identification numbers which were saved with the study numbers by the researchers. The results showed that burnout consists of three separate but correlating symptoms: exhaustion, cynicism and lack of professional efficacy. As a syndrome, burnout was strongly related to job stressors at work, and seemed to develop from exhaustion through cynicism to lack of professional efficacy in a similar manner among white-collar and blue-collar employees. The results also showed that exhaustion persisted even after eight years of follow-up but did not predict cynicism or lack of professional efficacy after that amount of time. Nor were job stressors longitudinally related to burnout. Longitudinal results were obtained for the severe health-related consequences of burnout. The investigated outcomes represented different phases of health deterioration ranging from sick-leaves and hospitalization periods to receiving work disability pensions. The results showed that burnout syndrome, and its elements of exhaustion and cynicism, were related to future mental and cardiovascular disorders as indicated by hospitalization periods. Burnout was also related to future sick-leave periods due to mental, cardiovascular and musculoskeletal disorders. Of the separate elements, exhaustion was related to the same three categories of disorder, cynicism to mental, musculoskeletal and digestive disorders, and lack of professional efficacy to mental and musculoskeletal disorders. Burnout also predicted receiving disability pensions due to mental and musculoskeletal disorders among initially healthy subjects. Exhaustion was related to receiving disability pensions even when self-reported chronic illness was taken into account. The results suggest that burnout is a multidimensional, chronic, work-related syndrome, which may have serious consequences for health and work ability.

Social and material deprivation among youth in Finland : causes, consequences, and coping.

Background: Social and material deprivation is associated with poor health, decreased subjective well-being, and limited opportunities for personal development. To date, little is known about the lived experiences of Finnish low-income youths and the general purpose of this study is to fill this gap. Despite the extensive research on socioeconomic income disparities, only a few scholars have addressed the question of how low socioeconomic position is experienced by disadvantaged people themselves. Little is known about the everyday social processes that lead to decreased well-being of economically and socially disadvantaged citizens. Data: The study is based on the data of 65 autobiographical essays written by Finnish low-income youths aged 14-29 (M=23.51, SD=3.95). The research data were originally collected in a Finnish nationwide writing contest “Arkipäivän kokemuksia köyhyydestä” [Everyday Experiences of Poverty] between June and September of 2006. The contest was partaken by 850 Finnish writers. Methods and key concepts: Autobiographical narratives (N=65) of low-income youths were analyzed based on grounded theory methodology (GTM). The analysis was not built on specific pre-conceived categorizations; it was guided by the paradigm model and so-called “sensitizing concepts”. The concepts this study utilized were based on the research literature on socioeconomic inequalities, resilience, and coping. Socioeconomic inequalities refer to unequal distribution of resources, such as income, social status, and health, between social groups. The concept of resilience refers to an individual’s capacity to cope despite existing risk factors and conditions that are harmful to health and well-being. Coping strategies can be understood as ways by which a person tries to cope with psychological stress in a situation where internal or externals demands exceed one’s resources. The ways to cope are cognitive or behavioral efforts by which individual tries to relieve the stress and gain new resources. Lack of material and social resources is associated with increased exposure to health-related stressors during the life-course. Aims: The first aim of this study is to illustrate how youths with low socioeconomic status perceive the causes and consequences of their social and material deprivation. The second aim is to describe what kind of coping strategies youths employ to cope in their everyday life. The third aim is to build an integrative conceptual framework based on the relationships between causes, consequences, and individual coping strategies associated with deprivation. The analysis was carried out through systematic coding and orderly treatment of the data based on the grounded theory methodology. Results: Finnish low-income youths attributed the primary causes of deprivation to their family background, current socioeconomic status, sudden life changes, and contextual factors. Material and social deprivation was associated with various kinds of negative psychological, social, and material consequences. Youths used a variety of coping strategies that were identified as psychological, social, material, and functional-behavioral. Finally, a conceptual framework was formulated to link the findings together. In the discussion, the results were compared and contrasted to the existing research literature. The main references of the study were: Coping: Aldwin (2007); Lazarus & Folkman (1984); Hobfoll (1989, 2001, 2002). Deprivation: Larivaara, Isola, & Mikkonen (2007); Lister (2004); Townsend (1987); Raphael (2007). Health inequalities: Dahlgren & Whitehead (2007); Lynch. et al. (2000); Marmot & Wilkinson (2006); WHO (2008). Methods: Charmaz (2006); Flick (2009); Strauss & Corbin (1990). Resilience: Cutuli & Masten (2009); Luthar (2006).