BACKGROUND AND PURPOSE—Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple ...types of small vessel disease–related brain changes and examined their individual and combined predictive value on cognitive and functional abilities.
METHODS—Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network–based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years.
RESULTS—The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (P<0.001 for global cognitive function, processing speed, executive functions, and memory and P<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes (P<0.001) even above the contribution of the individual brain changes.
CONCLUSIONS—Global burden of small vessel disease–related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.
In this narrative study, we explored the meaning infertile women attribute to social support in coping with their infertility-related challenges. Written accounts and episodic interviews with 26 ...previously infertile Finnish women were used as data. Two different coping story types emerged: coping alone and coping with support. In the coping alone type women neither sought nor received support. Their coping appeared as a lonely struggle. In the coping with stories, women turned to their spouses, peers, or professionals, but still emphasized that they would have needed more support. Based on our findings, we underline the need for individually tailored support.
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DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
3.
Dali server update Holm, Liisa; Laakso, Laura M
Nucleic acids research,
07/2016, Volume:
44, Issue:
W1
Journal Article
Peer reviewed
Open access
The Dali server (http://ekhidna2.biocenter.helsinki.fi/dali) is a network service for comparing protein structures in 3D. In favourable cases, comparing 3D structures may reveal biologically ...interesting similarities that are not detectable by comparing sequences. The Dali server has been running in various places for over 20 years and is used routinely by crystallographers on newly solved structures. The latest update of the server provides enhanced analytics for the study of sequence and structure conservation. The server performs three types of structure comparisons: (i) Protein Data Bank (PDB) search compares one query structure against those in the PDB and returns a list of similar structures; (ii) pairwise comparison compares one query structure against a list of structures specified by the user; and (iii) all against all structure comparison returns a structural similarity matrix, a dendrogram and a multidimensional scaling projection of a set of structures specified by the user. Structural superimpositions are visualized using the Java-free WebGL viewer PV. The structural alignment view is enhanced by sequence similarity searches against Uniprot. The combined structure-sequence alignment information is compressed to a stack of aligned sequence logos. In the stack, each structure is structurally aligned to the query protein and represented by a sequence logo.
Cardiovascular disease (coronary heart disease, stroke, peripheral vascular disease) is the most important cause of mortality and morbidity among patients with type 2 diabetes. Conventional risk ...factors contribute similarly to macrovascular complications in patients with type 2 diabetes and nondiabetic subjects, and therefore, other explanations have been sought for enhanced atherothrombosis in type 2 diabetes. Among characteristics specific for type 2 diabetes, hyperglycemia has recently been a focus of keen research. A recent meta-analysis of 20 studies on nondiabetic subjects has demonstrated that in the nondiabetic range of glycemia (<6.1 mmol/l), increased glucose is already associated with an increased risk for cardiovascular disease. Similarly, 12 recent prospective studies have convincingly indicated that hyperglycemia contributes to cardiovascular complications in patients with type 2 diabetes. The recently published U.K. Prospective Diabetes Study has shown that intensive glucose control reduces effectively microvascular complications among patients with type 2 diabetes, but that its effect on the prevention of cardiovascular complications was limited. Given the fact that in the U.K. Prospective Diabetes Study, none of the treatment modalities was particularly effective in reducing glucose, this underestimates the true potential of the correction of hyperglycemia in the prevention of cardiovascular disease in type 2 diabetes. However, in addition to intensive therapy of hyperglycemia, other conventional risk factors should also be normalized to prevent cardiovascular disease in patients with type 2 diabetes.
Objectives
The aim of this study was to characterize diabetes risk in relation to amount and distribution of body fat (environmental factors) and genetic risk defined as having first‐degree (FH1) or ...second‐degree relatives with diabetes.
Design
We analysed the METSIM population of 10 197 middle‐aged, randomly selected men. At baseline, information about family history of diabetes was registered and all individuals underwent extensive phenotyping. A follow‐up study was conducted after 6 years. The metabolic consequences of increased visceral versus subcutaneous fat were characterized in a separate cohort of 158 healthy men (the Kuopio Cohort of the EUGENE2 study).
Results
At baseline, individuals with a family history of diabetes (FH+) had approximately a twofold increase in the prevalence of type 2 diabetes compared with individuals without a family history of the disease (FH−) (18.0% vs. 9.9%; P = 1.3 × 10−31). FH1 individuals were more commonly overweight and obese compared with FH− (69.2% vs. 64.8%; P = 1.3 × 10−4) and, for a given body mass index, showed an increased risk profile for both type 2 diabetes and cardiovascular disease as well as a greater susceptibility to the negative consequences of increased body fat also when nonobese. Subgroup analyses indicated that the metabolic consequences were due primarily to increased ectopic/visceral fat rather than subcutaneous fat. The increased risk profile in FH+ individuals was not altered by adjusting for 43 major diabetes risk genes.
Conclusions
Family history of type 2 diabetes (particularly FH1) is associated with both increased risk of becoming overweight/obese and with a greater susceptibility to the negative consequences of increasing body fat, probably as a consequence of an increased propensity to accumulate ectopic (nonsubcutaneous) fat.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Type 2 diabetes increases the risk of cardiovascular disease (CVD) two- to fourfold compared with the risk in non-diabetic subjects. Although type 2 diabetes is associated with a clustering of risk ...factors (small, dense low-density lipoprotein LDL particles, low high-density lipoprotein HDL cholesterol, high triglycerides, elevated blood pressure, obesity, central obesity, hyperinsulinaemia, hyperglycaemia, etc.), the cause for an excess risk of CVD remains unknown. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol and blood pressure is similarly beneficial in diabetic and non-diabetic subjects. The treatment of hyperglycaemia reduces micro- and macrovascular complications in type 2 diabetic patients. Beta-blocking agents, angiotensin-converting enzyme inhibitors, aspirin, and thrombolytic therapy are also effective in the treatment of CVD amongst diabetic patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objectives: To test the applicability of an automated method of magnetic resonance image analysis (voxel based morphometry) to detect presence and severity of regional grey matter density reduction—a ...proxy of atrophy—in Alzheimer's disease. Methods: Twenty nine probable Alzheimer's patients and 26 non-demented controls (mini-mental state examinations mean (SD) 21 (4) and 29 (1)) underwent high resolution 3D brain magnetic resonance imaging. Spatial normalisation to a stereotactic template, segmentation into grey matter, white matter, and cerebrospinal fluid, and smoothing of the grey matter were carried out based on statistical parametric mapping (SPM99) algorithms. Analyses were carried out: (a) contrasting all Alzheimer's patients with all controls (p<0.05 corrected for multiple comparisons); (b) contrasting the three Alzheimer's patients with mini-mental state of 26 and higher with all controls (p<0.0001 uncorrected); and (c) correlating grey matter density with mini-mental state score within the Alzheimer's group (p<0.0001 uncorrected). Results: When all Alzheimer's patients were compared with controls, the largest atrophic regions corresponded to the right and left hippocampal/amygdalar complex. All parts of the hippocampus (head, body, and tail) were affected. More localised atrophic regions were in the temporal and cingulate gyri, precuneus, insular cortex, caudate nucleus, and frontal cortex. When the mildest Alzheimer's patients were contrasted with controls, the hippocampal/amygdalar complex were again found significantly atrophic bilaterally. The mini-mental state score correlated with grey matter density reduction in the temporal and posterior cingulate gyri, and precuneus, mainly to the right. Conclusions: Voxel based morphometry with statistical parametric mapping is sensitive to regional grey matter density reduction in mild Alzheimer's disease.
OBJECTIVES To explore volume changes of the entorhinal cortex (ERC) and hippocampus in mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with normal cognition (NC); to determine ...the powers of the ERC and the hippocampus for discrimination between these groups. METHODS This study included 40 subjects with NC, 36 patients with MCI, and 29 patients with AD. Volumes of the ERC and hippocampus were manually measured based on coronal T1 weighted MR images. Global cerebral changes were assessed using semiautomatic image segmentation. RESULTS Both ERC and hippocampal volumes were reduced in MCI (ERC 13%, hippocampus 11%, p<0.05) and AD (ERC 39%, hippocampus 27%, p<0.01) compared with NC. Furthermore, AD showed greater volume losses in the ERC than in the hippocampus (p<0.01). In addition, AD and MCI also had cortical grey matter loss (p< 0.01) and ventricular enlargement (p<0.01) when compared with NC. There was a significant correlation between ERC and hippocampal volumes in MCI and AD (both p<0.001), but not in NC. Using ERC and hippocampus together improved discrimination between AD and CN but did not improve discrimination between MCI and NC. The ERC was better than the hippocampus for distinguishing MCI from AD. In addition, loss of cortical grey matter significantly contributed to the hippocampus for discriminating MCI and AD from NC. CONCLUSIONS Volume reductions in the ERC and hippocampus may be early signs of AD pathology that can be measured using MRI.
Background: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer ...an increased risk of progressing to dementia and most often Alzheimer’s disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. Objective: To study the pattern of brain atrophy in MCI. Methods: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p<0.001. Results: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere—for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. Conclusions: The MRI findings in MCI resemble those seen in early AD.
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