| 1. |
- Koivula, Robert, et al.
(författare)
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Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes : rationale and design of the epidemiological studies within the IMI DIRECT Consortium
- 2014
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 57:6, s. 1132-1142
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS:The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT.METHODS:Prediabetic participants (target sample size 2,200-2,700) and patients with newly diagnosed type 2 diabetes (target sample size ~1,000) are undergoing detailed metabolic phenotyping at baseline and 18 months and 36 months later. Abdominal, pancreatic and liver fat is assessed using MRI. Insulin secretion and action are assessed using frequently sampled OGTTs in non-diabetic participants, and frequently sampled mixed-meal tolerance tests in patients with type 2 diabetes. Biosamples include venous blood, faeces, urine and nail clippings, which, among other biochemical analyses, will be characterised at genetic, transcriptomic, metabolomic, proteomic and metagenomic levels. Lifestyle is assessed using high-resolution triaxial accelerometry, 24 h diet record, and food habit questionnaires.CONCLUSIONS/INTERPRETATION:DIRECT will yield an unprecedented array of biomaterials and data. This resource, available through managed access to scientists within and outside the Consortium, will facilitate the development of new treatments and therapeutic strategies for the prevention and management of type 2 diabetes
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| 2. |
- Pyykko, Okko T., et al.
(författare)
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Incidence, Comorbidities, and Mortality in Idiopathic Normal Pressure Hydrocephalus
- 2018
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Ingår i: World Neurosurgery. - : ELSEVIER SCIENCE INC. - 1878-8750 .- 1878-8769. ; 112, s. E624-E631
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Tidskriftsartikel (refereegranskat)abstract
- OBJECT: To investigate the incidence, comorbidities, mortality, and causes of death in idiopathic normal pressure hydrocephalus (iNPH). METHODS: A cohort of 536 patients with possible NPH from a defined population with a median follow-up time of 5.1 years, (range 0.04-19.9 years) was included in the study. Patients were evaluated by brain imaging and intraventricular pressure monitoring, with a brain biopsy specimen immunostained against amyloid-beta and hyper-phosphorylated tau. Hospital records were reviewed for vascular diseases and type 2 diabetes mellitus (T2DM). Death certificates and yearly population of the catchment area were obtained from national registries. RESULTS: A total of 283 patients had a clinical diagnosis of iNPH, leading to a median annual incidence of 1.58 iNPH patients per 100,000 inhabitants (range, 0.8-4.5). Alzeimer disease-related brain biopsy findings were less frequent in iNPH patients than in non-iNPH patients (P < 0.05). An overrepresentation of hypertension (52% vs. 33%, P < 0.001) and T2DM (23% vs. 13%, P = 0.002) was noted in iNPH patients. Age (hazard ratio [HR] 1.04/year, 95% confidence interval [CI] 1.03-1.06, P< 0.001) and T2DM (HR 1.63, 95% CI 1.23-2.16, P < 0.001) increased the risk of death in the iNPH patients and in the total population. iNPH was associated with decreased risk of death (HR 0.63, 95% CI 0.50-0.78, P < 0.001). The most frequent causes of death were cardiovascular and cerebrovascular disease. Dementia as a cause of death was more common in non-iNPH patients (27% vs. 10%, P < 0.001). CONCLUSIONS: Hypertension and T2DM are common in iNPH and the latter causes excess mortality in the affected patients.
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| 3. |
- Sandberg, Fredrik, 1976-, et al.
(författare)
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Problems and Possibilities in Recognition of Prior Learning : A Critical Social Theory Perspective
- 2014
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Ingår i: Promoting, assessing, recognizing and certifying lifelong learning. - Dordrecht : Springer. - 9789401786935 - 9789401786942 ; , s. 235-248
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter argues for the importance of understanding recognition of prior learning (RPL) through the critical social theories of Jürgen Habermas and Axel Honneth. Results from a research project exploring RPL for the accreditation of prior experiential learning in the healthcare sector in Sweden are used to develop the analysis. It is argued that RPL for accreditation could, by reflecting the results of Habermas’ theory of communicative action, be a process that strengthens social integration and solidarity and develops personal identity. RPL could encourage critical learning in the lifeworld of education through reflections on prior learning, experiences and knowledge gained in work. It is important that the results of the RPL process and assessment are clearly communicated. This would enable these experiences to be mobilised when students move on and use these learning experiences in new contexts. Honneth’s recognition theory can further help us understand what impact the recognition in RPL could have for an individual’s self-esteem development and how RPL processes can support self-realisation.
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| 4. |
- Uusitalo, Karoliina, et al.
(författare)
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Preterm children's developmental coordination disorder, cognition and quality of life : a prospective cohort study
- 2020
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Ingår i: BMJ Paediatrics Open. - : BMJ. - 2399-9772. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo evaluate the rate of developmental coordination disorder (DCD) and its correlation to cognition and self-experienced health-related quality of life (HRQoL) in children born very preterm.DesignProspective follow-up study.SettingRegional population of children born very preterm in Turku University Hospital, Finland, in 2001-2006.PatientsA total of 170 children born very preterm were followed up until 11 years of age.Main outcome measuresMotor and cognitive outcomes were evaluated using the Movement Assessment Battery for Children - Second Edition (Movement ABC-2) and the Wechsler Intelligence Scale for Children - Fourth Edition, respectively, and HRQoL using the 17-Dimensional Illustrated Questionnaire (17D). The Touwen neurological examination was performed to exclude other neurological conditions affecting the motor outcome.ResultsEighteen children born very preterm (17 boys) (11.3%) had DCD, defined as Movement ABC-2 total test score <= 5th percentile. A positive correlation between motor and cognitive outcome (r=0.22, p=0.006) was found. Children born very preterm with DCD had lower cognitive scores than those without DCD (Full-Scale IQ mean 76.8 vs 91.6, p=0.001). Moreover, children born very preterm with DCD reported lower HRQoL than children born very preterm without motor impairment (17D mean 0.93 vs 0.96, p=0.03). However, HRQoL was higher in this group of children born very preterm compared with population-based normative test results (p<0.001).ConclusionsDCD was still common at 11 years of age in children born very preterm in 2000s. DCD associated with adverse cognitive development and lower self-experienced HRQoL. However, this group of children born very preterm reported better HRQoL in comparison with Finnish norms.
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| 5. |
- Vanaveski, Taavi, et al.
(författare)
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PGC-1 alpha Signaling Increases GABA(A) Receptor Subunit alpha 2 Expression, GABAergic Neurotransmission and Anxiety-Like Behavior in Mice
- 2021
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Ingår i: Frontiers in Molecular Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5099. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a master regulator of mitochondria biogenesis and cell stress playing a role in metabolic and degenerative diseases. In the brain PGC-1 alpha expression has been localized mainly to GABAergic interneurons but its overall role is not fully understood. We observed here that the protein levels of gamma-aminobutyric acid (GABA) type A receptor-alpha 2 subunit (GABAR alpha 2) were increased in hippocampus and brain cortex in transgenic (Tg) mice overexpressing PGC-1 alpha in neurons. Along with this, GABAR alpha 2 expression was enhanced in the hippocampus of the PGC-1 alpha Tg mice, as shown by quantitative PCR. Double immunostaining revealed that GABAR alpha 2 co-localized with the synaptic protein gephyrin in higher amounts in the striatum radiatum layer of the hippocampal CA1 region in the Tg compared with Wt mice. Electrophysiology revealed that the frequency of spontaneous and miniature inhibitory postsynaptic currents (mIPSCs) was increased in the CA1 region in the Tg mice, indicative of an augmented GABAergic transmission. Behavioral tests revealed an increase for anxiety-like behavior in the PGC-1 alpha Tg mice compared with controls. To study whether drugs acting on PPAR gamma can affect GABAR alpha 2, we employed pioglitazone that elevated GABAR alpha 2 expression in primary cultured neurons. Similar results were obtained using the specific PPAR gamma agonist, N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L-tyrosine hydrate (GW1929). These results demonstrate that PGC-1 alpha regulates GABAR alpha 2 subunits and GABAergic neurotransmission in the hippocampus with behavioral consequences. This indicates further that drugs like pioglitazone, widely used in the treatment of type 2 diabetes, can influence GABAR alpha 2 expression via the PPAR gamma/PGC-1 alpha system.
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