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  • Gideon Neba, Shu (Helsingfors universitet, 2013)
    This study quantified above-ground biomass affected by selective logging in the tropical rainforest of South East Cameroon and also investigated the suitability of the density of logging roads, the density of log yards as well as variables from MODIS 250 m data (Red, NIR, MIR, NDVI, EVI) in explaining above-ground biomass logged. Above-ground biomass logged was quantified using allometric equations. The surface area of logging roads and log yards were quantified and used in the determination of above-ground biomass affected by these infrastructures based on a national reference baseline value for the forest zone of Cameroon. A comparative analysis revealed that 50% of potentially exploitable commercial tree species were effectively harvested with a harvesting intensity of 0.78 trees ha-1 representing an average above-ground biomass of 3.51 Mg ha-1. The results also indicated that 5.65 Mg ha-1 of above-ground biomass was affected by logging infrastructure .i.e. 62% as compared to 38% of above-ground biomass that was logged. Correlation and regression analysis showed that the density of the logging roads explained 66% of the variation in above-ground biomass logged and 73% of the variation in above-ground biomass logged was explained by the density of the logging roads and NDVI from MODIS data. The density of log yards and the variables from MODIS data were generally weak in explaining the variation in above-ground biomass logged.
  • Hielm-Björkman, Anna (Helsingin yliopisto, 2007)
    The series of investigations presented in this thesis examined different methods of assessing chronic pain in dogs suffering from osteoarthritis (OA) and compared the effects of three different treatments. Data were obtained from two cohorts; 41 dogs with OA due to canine hip dysplasia (CHD) (I,III) and 61 dogs with OA due to CHD or elbow dysplasia (II,IV,V). Questionnaires, veterinary evaluations, visual analog scales (VAS), plasma hormones, radiographs, and force plate evaluations were assessed as OA treatment outcome measures and/or measurements of chronic pain. The results indicated that the multidimensional pain scale including 11 questions with 5-point scale responses was a valid and reliable tool for evaluating chronic pain. This Helsinki chronic pain index (HCPI) can be applied as an outcome measure in clinical trials where chronic pain is evaluated by owners. Of the evaluated complementary therapies for chronic pain due to OA, all three indicated a positive treatment outcome. In the first trial, gold bead implants resulted in a significant positive treatment outcome for the treatment group. However, the placebo group in this study also improved significantly. A positive effect was seen in 65% of the placebo dogs and this exceptionally high incidence of amelioration suggests that the placebo group may have got an effect of unintentional needle acupuncture. The results of this study are therefore controversial and treatment guidelines based on these findings cannot be given. The second trial tested two ingestible OA remedies, green lipped mussel and a homeopathic low-dose combination preparation. Both treatments resulted in statistically significant positive treatment outcomes compared with placebo, but with the positive control (carprofen) being more effective than either of them. The results suggest that both tested treatments may be beneficial for chronic OA. To establish the true role of all these three treatments in outcome-based animal analgesia, more clinical trials, using larger cohorts, should be conducted. Possible mechanisms of action should also be studied.
  • Kiiski, Kirsi (Helsingin yliopisto, 2015)
    Nemaline myopathy (NM) and related disorders constitute a heterogeneous group of congenital myopathies. Mutations in the nebulin gene (NEB) are the main cause of the recessively inherited form. NEB is one of the largest genes in the human genome consisting of 249 kb of genomic sequence. NEB contains 183 exons and a 32 kb homologous triplicate region (TRI) where eight exons are repeated three times. The aims of this Doctoral Thesis study were to develop and implement into diagnostics new efficient variant analysis methods for NEB and other NM-causing genes. The first aim was to design and validate a custom copy number microarray targeting the NM-causing genes for the detection of copy number variations. MLPA (multiplex ligation-dependent probe amplification) and Sanger sequencing were also used. The second aim was to utilise whole-exome sequencing to search for novel disease-causing variants in the known NM genes and try to identify novel NM genes. Lastly, the aim was to collect more data in order to try to find genotype-phenotype correlations of NEB-caused NM. The design and validation of the NM-CGH microarray was successful. Of the total sample cohort of 356 NM families, 196 NM families were studied using the custom-made NM-CGH array. Nine different novel large causative variants were identified in ten NM families. The size of these variants varies greatly, covering only a part of one NEB exon on up to dozens of NEB exons (72bp - 133 kb). In addition, a novel recurrent variation of the NEB TRI region was identified in 13% of the NM families and in 10% of the studied 60 control samples. Deviations of one copy are suggested to be benign but gains of two or more copies might be pathogenic. One novel homozygous deletion was also identified in another NM gene, TPM3, in a patient with severe NM. Furthermore, ten samples were studied using exome sequencing, and for six of those samples, novel disease-causing variant(s) were identified. Two variants were identified in one family in a novel, putative NM gene that is currently under further investigation. 165 NM families from the total cohort of 356 NM families have been identified thus far with two pathogenic NEB variants. Altogether 220 different pathogenic variants were identified in these 165 families, accentuating that the patients in the majority (84%) of the families are compound heterozygous for two different NEB variants. Most of the variants are small single nucleotide changes whereas large variants are more rare. However, copy number variations are much more frequent than previously thought: pathogenic copy number variants were identified in 16% of these 356 NM-families. Genotype-phenotype correlations between the type of NEB mutation and the NM subtypes remained, however, unobtainable. The NM-CGH microarray has been implemented into molecular diagnostics of NM. Using the NM-CGH microarray followed by exome-sequencing has accelerated mutation detection. This combination has increased the coverage of the NM genes and thus improved the diagnostics of NM and NM-related disorders.
  • Laakso, Hanna (Helsingin yliopisto, 2015)
    Objective: Cognitive impairment as a consequence of a stroke is common. Advanced age increases the frequency of poststroke cognitive deficits. Particularly executive dysfunction has an important role in poststroke disability. Complex by their nature, however, measuring executive function is difficult. The Hayling test, Design fluency task and Questioning task are some of the less common assessment methods of executive functions, and thus, they are not widely studied. The aim of the present study was to assess the feasibility of these tests in elderly patients three months after ischemic stroke. Performances on these tests were compared to conventional assessment methods of executive functions, and their predictive value on functional disability in follow-up was examined. Methods: 62 stroke patients and 39 control subjects, aged 55-85, underwent comprehensive neurological and neuropsychological examinations three months after the index stroke. Executive functions were studied with the Trail Making test, Stroop test, Wisconsin card sorting test, Verbal fluency task as well as with the Hayling test, Design fluency task and Questioning task. The modified Rankin Scale (mRS) and the Lawton’s Instrumental activities of daily living -scale (IADL) were used to assess functional abilities at three months, and the mRS after 15 months follow-up. Results and conclusions: The Hayling test and Questioning task and the four conventional tests of executive functions differentiated stroke patients from healthy controls. Furthermore, the executive functions predicted functional dependence in the elderly stroke patients. The Hayling test was most consistently associated with functional disability as evaluated with mRS and IADL three months after the stroke, and predicted functional disability as evaluated with mRS at 15 months follow-up. Of all executive functions tests, the Hayling test proved to be the most constant predictor of functional abilities in elderly stroke patients. However, there is no golden standard for measuring executive functions, and in the future, more sensitive methods are needed. Nevertheless, the present study confirms the importance of assessing executive functions in clinical populations, when predicting functional disability even in the long-term.
  • Järvinen, Päivi (Helsingin yliopisto, 2011)
    The first line medication for mild to moderate Alzheimer s disease (AD) is based on cholinesterase inhibitors which prolong the effect of the neurotransmitter acetylcholine in cholinergic nerve synapses which relieves the symptoms of the disease. Implications of cholinesterases involvement in disease modifying processes has increased interest in this research area. The drug discovery and development process is a long and expensive process that takes on average 13.5 years and costs approximately 0.9 billion US dollars. Drug attritions in the clinical phases are common due to several reasons, e.g., poor bioavailability of compounds leading to low efficacy or toxic effects. Thus, improvements in the early drug discovery process are needed to create highly potent non-toxic compounds with predicted drug-like properties. Nature has been a good source for the discovery of new medicines accounting for around half of the new drugs approved to market during the last three decades. These compounds are direct isolates from the nature, their synthetic derivatives or natural mimics. Synthetic chemistry is an alternative way to produce compounds for drug discovery purposes. Both sources have pros and cons. The screening of new bioactive compounds in vitro is based on assaying compound libraries against targets. Assay set-up has to be adapted and validated for each screen to produce high quality data. Depending on the size of the library, miniaturization and automation are often requirements to reduce solvent and compound amounts and fasten the process. In this contribution, natural extract, natural pure compound and synthetic compound libraries were assessed as sources for new bioactive compounds. The libraries were screened primarily for acetylcholinesterase inhibitory effect and secondarily for butyrylcholinesterase inhibitory effect. To be able to screen the libraries, two assays were evaluated as screening tools and adapted to be compatible with special features of each library. The assays were validated to create high quality data. Cholinesterase inhibitors with various potencies and selectivity were found in natural product and synthetic compound libraries which indicates that the two sources complement each other. It is acknowledged that natural compounds differ structurally from compounds in synthetic compound libraries which further support the view of complementation especially if a high diversity of structures is the criterion for selection of compounds in a library.
  • Kylmälä, Minna (Helsingin yliopisto, 2014)
    Myocardial infarct size is clinically relevant, affecting heart function and patient prognosis. After myocardial infarction (MI), it is important to establish whether myocardial dysfunction is due to permanent infarct damage, or if the myocardium is viable, in which case contraction may be improved by revascularization. Established methods for assessing infarct size and viability, such as cardiac magnetic resonance imaging with delayed contrast enhancement (DE-CMR) and myocardial perfusion imaging are neither readily available nor suitable in acute MI. In contrast, electrocardiography (ECG) and echocardiography are widely available diagnostic methods at the patient’s bedside at any hour. Echocardiographic strain rate imaging, based on measurement of myocardial velocities by tissue Doppler, is a sensitive and objective method for quantification of myocardial contraction. If myocardium contracts, it is viable. Body surface potential mapping (BSPM) records ECG with multiple leads covering the entire thorax, with a variety of ECG variables automatically calculated from its recordings. The aim of the studies for this thesis was to evaluate whether infarct size and myocardial viability can be assessed by strain rate imaging and BSPM. The studies included up to 57 patients with acute coronary syndrome, most with an infarction. BSPM with 123 leads and echocardiography were performed within 48 hours after onset of chest pain, and repeated during recovery of the infarction, at 1 to 4 weeks, and after healing, at 6 to 12 months. Global infarct size and segmental extent of infarct were determined by DE-CMR after healing. Strain rate imaging allowed assessment of viability and global infarct size in both acute and chronic MI. Strain mapping was validated, for the first time, as a semi-quantitative method for the assessment of systolic strain, and showed excellent correlation with quantitative strain values. In chronic MI, segments with systolic strain values less than -6% were most probably viable, having no infarct or a non-transmural infarct. Strain mapping proved as good as quantitative strain in distinguishing transmural from non-transmural infarcts. In acute MI, strain- and strain-rate variables could distinguish viable from non-viable segments, post-systolic strain having the best accuracy at predicting recovery of severe contraction abnormality (AUC 0.78). BSPM could estimate infarct size at all stages of the infarction, with Q- and R-wave variables, as well as the QRS integral having the strongest correlations with infarct size at all time-points. The repolarization variables were clearly inferior; only in chronic MI did the T-wave variables have nearly as strong correlations with infarct size as did QRS variables. In contrast, the repolarization variables proved good at predicting recovery of left ventricular (LV) function in acute MI, irrespective of MI location. The 1st QRS integral was the only depolarization variable good at predicting recovery of LV dysfunction, and the only variable able to estimate infarct size in addition to viability. In conclusion, strain rate imaging as well as computed ECG variables can predict recovery of myocardial function in acute MI and can assess infarct size in both acute and chronic MI. Strain values can be quickly and accurately estimated by the strain-mapping method, validated now for the first time in the assessment of infarct transmurality. These methods, easily performed at bedside, may help the clinician assess patient prognosis and the need for revascularization after MI.
  • Janno, Sven (Helsingin yliopisto, 2006)
    The prevalence and assessment of neuroleptic-induced movement disorders (NIMDs) in a naturalistic schizophrenia population that uses conventional neuroleptics were studied. We recruited 99 chronic schizophrenic institutionalized adult patients from a state nursing home in central Estonia. The total prevalence of NIMDs according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) was 61.6%, and 22.2% had more than one NIMD. We explored the reliability and validity of different instruments for measuring these disorders. First, we compared DSM-IV with the established observer rating scales of Barnes Akathisia Rating Scale (BARS), Simpson-Angus Scale (SAS) (for neuroleptic-induced parkinsonism, NIP) and Abnormal Involuntary Movement Scale (AIMS) (for tardive dyskinesia), all three of which have been used for diagnosing NIMD. We found a good overlap of cases for neuroleptic-induced akathisia (NIA) and tardive dyskinesia (TD) but somewhat poorer overlap for NIP, for which we suggest raising the commonly used threshold value of 0.3 to 0.65. Second, we compared the established observer rating scales with an objective motor measurement, namely controlled rest lower limb activity measured by actometry. Actometry supported the validity of BARS and SAS, but it could not be used alone in this naturalistic population with several co-existing NIMDs. It could not differentiate the disorders from each other. Quantitative actometry may be useful in measuring changes in NIA and NIP severity, in situations where the diagnosis has been made using another method. Third, after the relative failure of quantitative actometry to show diagnostic power in a naturalistic population, we explored descriptive ways of analysing actometric data, and demonstrated diagnostic power pooled NIA and pseudoakathisia (PsA) in our population. A subjective question concerning movement problems was able to discriminate NIA patients from all other subjects. Answers to this question were not selective for other NIMDs. Chronic schizophrenia populations are common worldwide, NIMD affected two-thirds of our study population. Prevention, diagnosis and treatment of NIMDs warrant more attention, especially in countries where typical antipsychotics are frequently used. Our study supported the validity and reliability of DSM-IV diagnostic criteria for NIMD in comparison with established rating scales and actometry. SAS can be used with minor modifications for screening purposes. Controlled rest lower limb actometry was not diagnostically specific in our naturalistic population with several co-morbid NIMDs, but it may be sensitive in measuring changes in NIMDs.
  • Holi, Matti (Helsingin yliopisto, 2003)
  • Siljander, Heli (Helsingin yliopisto, 2010)
    Background and aims. Type 1 diabetes (T1D), an autoimmune disease in which the insulin producing beta cells are gradually destroyed, is preceded by a prodromal phase characterized by appearance of diabetes-associated autoantibodies in circulation. Both the timing of the appearance of autoantibodies and their quality have been used in the prediction of T1D among first-degree relatives of diabetic patients (FDRs). So far, no general strategies for identifying individuals at increased disease risk in the general population have been established, although the majority of new cases originate in this population. The current work aimed at assessing the predictive role of diabetes-associated immunologic and metabolic risk factors in the general population, and comparing these factors with data obtained from studies on FDRs. Subjects and methods. Study subjects in the current work were subcohorts of participants of the Childhood Diabetes in Finland Study (DiMe; n=755), the Cardiovascular Risk in Young Finns Study (LASERI; n=3475), and the Finnish Type 1 Diabetes Prediction and Prevention Study (DIPP) Study subjects (n=7410). These children were observed for signs of beta-cell autoimmunity and progression to T1D, and the results obtained were compared between the FDRs and the general population cohorts. --- Results and conclusions. By combining HLA and autoantibody screening, T1D risks similar to those reported for autoantibody-positive FDRs are observed in the pediatric general population. Progression rate to T1D is high in genetically susceptible children with persistent multipositivity. Measurement of IAA affinity failed in stratifying the risk assessment in young IAA-positive children with HLA-conferred disease susceptibility, among whom affinity of IAA did not increase during the prediabetic period. Young age at seroconversion, increased weight-for-height, decreased early insulin response, and increased IAA and IA-2A levels predict T1D in young children with genetic disease susceptibility and signs of advanced beta-cell autoimmunity. Since the incidence of T1D continues to increase, efforts aimed at preventing T1D are important, and reliable disease prediction is needed both for intervention trials and for effective and safe preventive therapies in the future. Our observations confirmed that combined HLA-based screening and regular autoantibody measurements reveal similar disease risks in pediatric general population as those seen in prediabetic FDRs, and that risk assessment can be stratified further by studying glucose metabolism of prediabetic subjects. As these screening efforts are feasible in practice, the knowledge now obtained can be exploited while designing intervention trials aimed at secondary prevention of T1D.
  • Molander, Pauliina (Helsingin yliopisto, 2014)
    In the era of TNFα-blocking therapy, MH and even DR have been suggested as new therapeutic targets in both CD and UC. Recent studies have indicated that DR may be achieved in roughly half of IBD patients on TNFα-blocking maintenance therapy, resulting in more favorable treatment outcomes. However, considering the potential side-effects and economic issues associated with long-term immunosuppressive therapy with TNFα-blocking agents, the possibility of discontinuing therapy should be evaluated at least once after achieving DR. At present, no widely accepted recommendations for discontinuing TNFα-blocking therapy are available. Based on the results of our study, only for about half of patients in DR were candidates for discontinuation of TNF-blocking medication for various reasons. Nevertheless, up to 67% of IBD patients in DR at the time of cessation of TNFα-blocking therapy remained in clinical remission during the 12-month follow-up, and moreover, the majority of these patients also remained in endoscopic remission. Therefore, withdrawal of therapy could be considered in IBD patients in DR even after one-year treatment. Reassuringly, in case of a relapse, the response to restart of TNFα-blocking therapy seems to be effective and well-tolerated. To evaluate treatment response and possible relapse during maintenance therapy or after discontinuation of TNFα-blocking therapy, FC seems to be a reliable surrogate marker to replace endoscopic assessment. A normal FC after induction with TNFα-blocking agents predicts sustained remission in the majority of patients with active luminal disease receiving scheduled treatment. However, an objective cut-off value for treatment response and relapse risk is to some extent still undefined. To predict IBD relapse and identify patients requiring a close follow-up in clinical practice, FC seems to be a useful surrogate marker, as it increases and remains elevated as early as 6 months before symptomatic relapse. FC measurements should therefore be included in monitoring IBD patient s treatment response in everyday clinical practice.
  • Geneid, Ahmed (Helsingin yliopisto, 2013)
    Over the last decades, school teachers and singers have been more or less the focus of voice research, due to their specific occupational needs. Now, other population groups as well start to draw attention. These new groups include workers exposed to organic dusts in various workplaces with possible laryngeal reactions. The second group includes children operated on for subglottic stenosis with possible effects on voice and related quality of life. The third are nursery teachers insufficiently studied through field research for possible voice problems. This thesis aims to shed light on these newly emerging vulnerable groups in terms of assessing their voices through questionnaires, perceptual and acoustic voice assessment, and videolaryngoscopic examination. The thesis includes four studies. Nine subjects with suspected occupational rhinitis or asthma participated in Studies I and II. They had single blinded exposures to organic dust and placebo substances. Subjective and perceptual voice assessment was done in addition to acoustic analysis of 180 samples using glottal inverse filtering. In Study III, children s voices were perceptually assessed as well as their health- and voice-related quality of life. In Study IV, 119 female kindergarten teachers responded to a questionnaire on voice habits, voice symptoms, and impact of various working conditions on voice. In addition, videolaryngoscopy examinations took place in these teachers workplaces. Studies I and II showed that some self-assessed voice and throat symptoms changed significantly after organic dust exposure, although perceptual assessment failed to record these changes. However, inverse filtering analysis revealed changes that represent the ones reported by the subjects. In Study III, voice-related quality of life and perceptual assessment of the study group showed lower scores than the controls . Study IV showed that 71.5% of the teachers examined reported frequent strain on the voice. Organic findings were observed in 10.9% of the subjects and did not correlate with subjective voice symptoms. The thesis added new information on these high-risk groups, identifying an occupational voice-disorder risk group related to laryngeal reactions rather than voice abuse. It also added information on the long-term effects of surgery for subglottic stenosis in early infancy. Nevertheless, field videolaryngoscopy was quite accurate in determining the percentage of organic findings among nursery teachers.
  • Saarinen, Ilona (Helsingfors universitet, 2012)
    The aim of this retrospective case-control study was to investigate association between post-term pregnancy and ABO blood groups and Rhesus factor. The original data was derived from the Helsinki University Central Hospital over a 4-year period (n=58,036 deliveries). The data on ABO blood groups and Rhesus factors were collected from Weblab-database and combined with the original data. There were 378 cases (post-term) and 8,626 controls (gestational age 37+0 – 41+6) after data linkage. Statistical comparisons were performed using Chi-Square and Mann-Whitney U-tests. The association between blood groups and the length of the pregnancy was analyzed by binary unconditional logistic regression. The AB blood group, and especially AB+ blood group, was associated with 1.5- and 1.6-fold higher risk of post term pregnancy, respectively. The Rhesus factor was not associated with higher or lower risk. Thus, gravidas without anti-A, anti-B and anti-D antibodies seem to have the highest risk for postterm pregnancy.