| 15581. |
- Mathillas, Johan, 1980-
(författare)
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Dementia, depression and delirium in the very old : prevalences and associated factors
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Emotional suffering in old age is largely caused by a variety of psychiatric disorders which are often, however, undertreated and underrecognized. This leads to reduced quality of life and functional status and increased morbidity and mortality. Dementia, delirium and depression are common disorders in the very old, and are similar in several ways. All have multiple causes and are diagnosed by means of symptomatic criteria, are challenging to diagnose and difficult to differentiate from each other in the very old. They often coexist in the same individual, and may have common risk factors.The overall aim of this thesis was to add to our knowledge about threats to successful aging, by investigating the prevalences of dementia, depression and delirium, and factors associated with these three disorders. Further aims were to measure change over time in the prevalence of dementia and depression, respectively, and to investigate the risk factors for incident depression. This thesis uses the population-based Umeå85+/GErontological Regional DAtabase (GERDA) material.In 2000-2002, every other 85-year-old, all 90-year-olds and all people ≥95 years living in six municipalities in Västerbotten, Sweden were invited to participate, and in 2005-2007 the process was repeated, with the additional inclusion of the corresponding populations of two municipalities in Österbotten, Finland. A third data collection was carried out in 2010-2012. Trained assessors carried out assessments in the form of structured interviews during one or more home visits, recorded current medication and reviewed medical records obtained from general practitioners and hospitals. In 2000-2002 the prevalence of dementia was 17% among 85-year-olds, 24% among 90-year-olds and 46% among those aged ≥95 years. In 2005-2007 dementia prevalence reached 28% among 85-year-olds, 40% among 90-yearolds and 45% among those aged ≥95 years. The prevalence of dementia in the total sample was 27% in 2000-2002 and 37% in 2005-2007 (p=0.001). In 2000-2002 the prevalence of depressive disorders was 24% among 85-yearolds, 34% among 90-year-olds and 31% among those aged ≥95 years. In 2005-2007 the prevalence of depressive disorders was 33% among 85-year-olds, 39% among 90-year-olds and 38% among those aged ≥95 years. The prevalence of depressive disorders in the total sample was 29% in 2000-2002 and 37% in 2005-2007 (p=0.025). Among participants not depressed at baseline, 26% had developed depression after five years. Factors independently associated with new cases of depression at follow-up were hypertension, a history of stroke and a higher score on the 15-item Geriatric Depression Scale at baseline. The thirtyday prevalence of delirium in 2005-2007 was 17% among 85-year-olds, 21% among 90-year-olds and 39% among participants aged ≥95 years. Delirium prevalence among individuals with dementia was higher than among those without dementia (52% vs. 5%, p<.001). Factors independently associated with delirium superimposed on dementia in a multivariate logistic regression model were depression, heart failure, living in an institution and prescribed antipsychotics.There was a high prevalence of dementia, depression and delirium in the papers comprising this thesis, and 55% had at least one of the three disorders. The prevalence of dementia and depression also increased between 2000-2002 and 2005-2007, after controlling for age and sex. Dementia and depression were important associated factors for delirium and half of those with dementia were depressed. The increasing age-specific prevalence of depression seems to be associated with the increasing age-specific prevalence of dementia. The papers presented are among the first to report a significantly increasing age-specific prevalence of dementia and depression among very old people. More knowledge about associated factors and risk factors concerning these disorders may be helpful for carers and decision-makers, as well as providing reference values for studies in other regions. Further efforts are needed in both care and research to better prevent, screen for, diagnose and treat dementia, depression and delirium, especially considering the growing number of very old people.
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| 15582. |
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| 15583. |
- Mathisen, Peter
(författare)
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Environmental factors selecting for predation resistant and potentially pathogenic bacteria in aquatic environments
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The long history of co-existence of bacteria and their protozoan predators in aquatic environments has led to evolution of protozoa resistant bacteria (PRB). Many of these bacteria are also pathogenic to humans. However, the ecological drivers determining the occurrence of different types of PRB in aquatic environments, and the eco-evolutionary link between bacterial adaptation and the resulting implications for mammalian hosts are poorly known. This thesis examines the impact of nutrients and predation on PRB, as well as the ecological and evolutionary connection between their life in aquatic environments and mammalian hosts. In the first study seven bacterial isolates from the Baltic Sea were investigated for their plasticity of adaptation to predation. The response to predation showed large variation where some bacteria rapidly developed a degree of grazing resistance when exposed to predators. The rapid adaptation observed may result in bacterial communities being resilient or resistant to predation, and thus rapid adaptation may be a structuring force in the food web. With the aim to elucidate the link between occurrence of PRB and environmental conditions, a field study and a laboratory experiment were performed. In both studies three PRB genera were found: Mycobacterium, Pseudomonas and Rickettsia. PRB were found both in oligotrophic and eutrophic waters, indicating that waters of all nutrient states can harbor pathogenic bacteria. However, the ecological strategy of the PRB varied depending on environmental nutrient level and disturbance. Using an advanced bioinformatic analysis, it was shown that ecotypes within the same PRB genus can be linked to specific environmental conditions or the presence of specific protozoa, cyanobacteria or phytoplankton taxa. These environmental conditions or specific plankton taxa could potentially act as indicators for occurrence of PRB. Finally, using four mutants (with specific protein deletions) of the pathogenic and predation resistant Francisella tularensis ssp. holarctica, I found evidence of an eco-evolutionary connection between the bacterium´s life in aquatic and mammalian hosts (aquatic amoeba Acanthamoeba castellanii and a murine macrophage). To a large extent F. t. holarctica use similar mechanisms to persist predation by protozoa and to resist degradation by mammal macrophages. To summarize I found a link between predation resistant bacteria in aquatic environments and bacteria that are pathogenic to mammals. Further, I showed that different environmental conditions rapidly selects for PRB with either intracellular or extracellular lifestyles. This thesis provides insights regarding environmental conditions and biomarkers that can be used for assessment of aquatic environments at risk for spreading pathogenic bacteria.
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| 15584. |
- Mathisen, Peter, et al.
(författare)
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Francisella tularensis subspecies holarctica´s adaptation to protozoan and mammal hosts
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The long co-existence of bacteria and protozoa in natural ecosystems has led to the evolution of different bacterial predation-resistance mechanisms1, which in turn may have triggered development of mammal pathogens2, such as the tularemia bacterium Francisella tularensis3. We studied links between environmental persistence and pathogenicity of Francisella tularensis subsp. holarctica (F. t. holarctica), by comparing its growth in association with an aquatic amoeba and a murine macrophage. A virulent wild-type strain and four isogenic mutations with different functional protein deletions were compared; DsbA4, 5 a membrane lipoprotein with disulfide oxidoreductase activity important for proper folding in Francisella tularensis; Hfq6 a pleiotropic regulatory RNA binding protein; PilA7, 8 a type IV pilus subunit and PglA9 a protein involved in O-linked protein glycosylation. DsbA was found to be essential for bacterial growth in association with both amoeba and macrophage, while PglA did not affect bacterial persistence in any of the hosts. Absence of PilA and Hfq had marked negative effect on the bacterial cell counts in amoeba, while growth was only slightly impaired in the macrophage. Functional similarities for bacterial persistence in both hosts highlight eco-evolutionary links between persistence of intracellular pathogenic bacteria in aquatic systems and mammal hosts.
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| 15585. |
- Matilda, Rentoft, 1981-
(författare)
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The use of formalin fixed paraffin embedded tissue and global gene expression profiling for increased understanding of squamous cell carcinoma of the tongue
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Head and neck cancer is the 6th most common malignancy worldwide, with tumours of the tongue being one of the most prevalent sites. Despite advances in surgery and radiotherapy, the five-year survival has not changed during the last decades and remains at approximately 50%. Identification of novel biomarkers for more personalized treatment is important for increasing survival in these patients. One of the most commonly used methods in the search for new biomarkers is microarray analysis. A substantial limitation with this technique is the requirement for fresh frozen samples from which high quality RNA can be extracted. This becomes particularly problematic when attempting to discover differences associated with individual sub-types or rare cancers. Recent developments, including the DASL microarray platform, have provided the possibility of analysing RNA of poorer quality from formalin fixed paraffin embedded (FFPE) samples. FFPE is the standard way of preserving tissue from patients and millions of samples are stored around the world. In this thesis we have evaluated the use of FFPE samples and global gene expression profiling for increasing basic knowledge in a subgroup of oral cancer patients with tumours of the tongue. As confirmation of microarray results using qPCR is of outmost importance for conclusive data evaluation, we first aimed at finding a housekeeping gene stably expressed across malignant and non-malignant FFPE oral tissue. TUBA6, which belongs to the tubulin family was detected as being the most stable out of eight possible genes and was thus used for qPCR normalization throughout the following studies. We have performed three separate microarray experiments. Initially only a focused DASL array covering 502 cancer related genes was available and we used it to analyze a smaller cohort of patients and controls (n=36). A similar cohort (n=29) was also analyzed for expression of 836 micoRNAs. In 2009 a whole genome DASL array was launched, covering over 20,000 genes, and all tongue tumour samples available between 1997 and 2010 (n=87) were analysed using this array. Similar to other research groups we observed very high replicate reproducibility using both DASL arrays. When using the microRNA array and the whole genome DASL array an effect of sample quality on the detected expression level of individual genes was noticed. While the expression of some genes severely decreased with a decrease in sample quality others were not changed. This will impair normalization, leading to a residual non-biological variation within the data. Based on our findings we have presented some recommendations for minimizing the effect of sample quality and maximizing the level of biologically relevant information obtained from these experiments, e.g. ensuring that samples in groups to be compared are of the same quality range. For the microRNA data we also introduced an additional normalization step to the standard normalizations. We could show that lists of differentially expressed genes generated when taking these precautions were enriched for genes involved in cancer related processes and contained for tongue carcinoma previously identified changes. A number of differentially expressed genes, novel for tongue carcinoma, were also confirmed in high quality fresh frozen samples, including BCL2A1 (apoptosis), CXCL10 (immune response), SLC2A6 (energy transport) and miR-424 (angiogenesis). In conclusion microarrays can be used to analyze FFPE samples but should be performed with care. Standard normalization methods will not remove the variation introduced by samples being of different quality, leading to spurious results. Taking a few precautions, however, led to the identification of differentially expressed genes relevant in tumour development and maintenance. The recommendations we make can facilitate design of future studies using FFPE samples. The genes we identified as being differentially expressed in tumour tissue now need to be further evaluated for their potential as biomarkers in tongue carcinoma.
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| 15586. |
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| 15587. |
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| 15588. |
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| 15589. |
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| 15590. |
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