| 1. |
- Andrén, Eva, et al.
(författare)
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Öppna prioriteringar inom nya områden : logopedi, nutritionsbedömning, habilitering och arbetsterapi
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det finns fortfarande ett behov av att öka kunskapen om och stödja den praktiska tillämpningen av riksdagens riktlinjer för öppna prioriteringar inom svensk hälso- och sjukvård. Flera förslag på hur ett sådant stöd kan se ut har tagits fram de senaste åren. Spridning av goda exempel är ett sådant förslag, metodstöd ett annat (PrioriteringsCentrum 2007). En mer påtaglig form av metodstöd är den nationella modell som vuxit fram för att konkretisera innebörden i riktlinjerna (Carlsson m fl 2007). Den får idag anses som välbeprövad inom ett flertal områden och har bidragit till att samsynen och kommunicerbarheten kring prioriteringar har ökat i landet. Erfarenheter visar dock att det behövs pedagogisk vägledning i hur modellen kan tillämpas. För att möta upp efterfrågan på sådant metodstöd erbjuder Prioriteringscentrum handledning i grupp. Den första handledningsgruppen är nu avslutad och det är deltagarnas prioriteringsarbeten som presenteras i denna rapport i syfte att sprida konkreta exempel på försök att tillämpa prioriteringsriktlinjerna.I rapporten presenteras fyra prioriteringsarbeten med fokus på: Regionsamverkan inom arbetsterapi Logopedi Yrkesspecifika prioriteringar på väg till teamet Från projekt till integrerat redskapExemplet med prioriteringar i regionsamverkan utgörs av det prioriteringsarbete som genomförts i det s k femklövernätverket bestående av en samverkansgrupp för arbetsterapeuter i ledningsposition på sjukhusen i Uppland, Västmanland, Södermanland, Gävleborg och Dalarna. Arbetet var ett försök att skapa gemensamma prioriteringar i regionen för ett sjukdomsområde som kändes relevant. Valet kom att falla på arbetsterapi inom reumatologi. Arbetet har sedan huvudsakligen bedrivits i en projektgrupp, bestående av en representant från varje sjukhus där arbetet växlat mellan arbete på hemmaplan och avstämningsträffar i projektgruppen.Försöket har visat att det finns en samsyn inom regionen kring prioriteringar inom arbetsterapi och reumatologi. Säkerheten i prioriteringarna har ökat i och med att fem arbetsterapiorganisationer tillsammans bidragit med ett stort underlagsmaterial bl a genom att delge varandra sina kliniska erfarenheter. Förutsättningarna för en mer likartad vård i regionen har ökat. Arbetet har också gett upphov till frågor om i vilka situationer det är att föredra att prioriteringsarbete bedrivs lokalt, regionvis och/eller nationellt.
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| 2. |
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| 3. |
- Björck, Lennart, et al.
(författare)
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Tveksam vinst med ekolantbruk
- 2009
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Ingår i: Svenska dagbladet. - 1101-2412. ; -
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 4. |
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| 5. |
- Fridjonsdottir, Elva, et al.
(författare)
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Mass spectrometry imaging identifies abnormally elevated brain L-DOPA levels and extrastriatal monoaminergic dysregulation in L-DOPA-induced dyskinesia
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- L-DOPA treatment for Parkinson's disease frequently leads to dyskinesias, the pathophysiology of which is poorly understood. We used MALDI-MSI to map the distribution of L-DOPA and monoaminergic pathways in brains of dyskinetic and nondyskinetic primates. We report elevated levels of L-DOPA, and its metabolite 3-O-methyldopa, in all measured brain regions of dyskinetic animals and increases in dopamine and metabolites in all regions analyzed except the striatum. In dyskinesia, dopamine levels correlated well with L-DOPA levels in extrastriatal regions, such as hippocampus, amygdala, bed nucleus of the stria terminalis, and cortical areas, but not in the striatum. Our results demonstrate that L-DOPA-induced dyskinesia is linked to a dysregulation of L-DOPA metabolism throughout the brain. The inability of extrastriatal brain areas to regulate the formation of dopamine during L-DOPA treatment introduces the potential of dopamine or even L-DOPA itself to modulate neuronal signaling widely across the brain, resulting in unwanted side effects.
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| 6. |
- Fridjonsdottir, Elva, et al.
(författare)
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Mass spectrometry imaging reveals brain-region specific changes in metabolism and acetylcholine levels in experimental Parkinson’s disease and L-DOPA-induced dyskinesia
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- There is evidence that cholinergic alterations are linked to various motor and non-motor symptoms of Parkinson’s disease. We therefore used mass spectrometry imaging to investigate regional changes in acetylcholine abundance in the brain of a non-human primate model of Parkinson’s disease (PD) and L-DOPA-induced dyskinesia (LID). We also present an experimental design for performing untargeted analysis using MALDI-MSI with multiple experiments incorporating quality control samples to monitor experimental variability. We observed that MPTP treatment (i) led to reductions in putaminal acetylcholine levels that persisted after L-DOPA treatment and (ii) appeared to induce a shift of choline metabolism from α-glycerophosphocholine towards betaine. LID animals exhibited reduced levels of various metabolites important for brain homeostasis including S-adenosylmethionine, glutathione, adenosine monophosphate, and acylcarnitines. The vasculature marker heme B was upregulated in the putamen of LID animals, suggesting increased blood-flow in the dyskinetic putamen. These results provide new insights into pathological choline-related metabolic changes in PD and LID.
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| 7. |
- Fridjonsdottir, Elva, et al.
(författare)
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Region-Specific and Age-Dependent Multitarget Effects of Acetylcholinesterase Inhibitor Tacrine on Comprehensive Neurotransmitter Systems
- 2022
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 17:1, s. 147-158
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Tidskriftsartikel (refereegranskat)abstract
- Regional brain distribution and metabolism of neurotransmitters and their response to drug treatment are fundamentally important for understanding the central effects of neuroactive substances. We used matrix-assisted laser desorption/ionization mass spectrometry imaging in combination with multivariate analysis to visualize in anatomical detail metabolic effects of aging and tacrine-mediated acetylcholinesterase inhibition on comprehensive neurotransmitter systems in multiple mouse brain regions of 12-week-old and 14-month-old mice. We detected age-related increases in 3,4-dihydroxyphenylacetaldehyde and histamine, indicating oxidative stress and aging deficits in astrocytes. Tacrine had a significant impact on the metabolism of neurotransmitters in both age groups; predominantly, there was an increased norepinephrine turnover throughout the brain and decreased 3-methoxy tyramine, a marker for dopamine release, in the striatum. The striatal levels of histamine were only elevated after tacrine administration in the older animals. Our results demonstrated that tacrine is a multitarget and region-specific neuroactive agent, inducing age-specific responses. Although well-studied, the complete mechanisms of the action of tacrine are not fully understood, and the current findings reveal features that may help explain its treatment-related effectiveness and central side effects.
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| 8. |
- Fälth Savitski, Maria, 1979-
(författare)
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Improved Neuropeptide Identification : Bioinformatics and Mass Spectrometry
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bioinformatic methods were developed for improved identification of endogenous peptides using mass spectrometry. As a framework for these methods, a database for endogenous peptides, SwePep, was created. It was designed for storing information about endogenous peptides including tandem mass spectra. SwePep can be used for identification and validation of endogenous peptides by comparing experimentally derived masses of peptides and their fragments with information in the database. To improve automatic peptide identification of neuropeptides, targeted sequence collections that better mimic the peptidomic sample was derived from the SwePep database. Three sequence collections were created: SwePep precursors, SwePep peptides, and SwePep predicted. The searches for neuropeptides performed against these three sequence collections were compared with searches performed against the entire mouse proteome, and it was observed that three times as many peptides were identified with the targeted SwePep sequence collections. Applying the targeted SwePep sequence collections to identification of previously uncharacterized peptides yielded 27 novel potentially bioactive neuropeptides.Two fragmentations studies were performed using high mass accuracy tandem mass spectra of tryptic peptides. For this purpose, two databases were created: SwedCAD and SwedECD for CID and ECD tandem mass spectra, respectively. In the first study, fragmentation pattern of peptides with missed cleaved sites was studied using SwedCAD. It was observed that peptides with two arginines positioned next to each other have the same ability to immobilize two protons as peptides with two distant arginines. In the second study, SwedECD was used for studying small neutral losses from the reduced species in ECD fragmentation. The neutral losses were characterized with regard to their specificity and sensitivity to function as reporter ions for revealing the presence of specific amino acids in the peptide sequence. The results from these two studies can be used to improve identification of both tryptic and endogenous peptides.In summary, a collection of methods was developed that greatly improved the sensitivity of mass spectrometry peptide identification.
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| 9. |
- He, Yachao, et al.
(författare)
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Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Prosaposin (PSAP) modulates glycosphingolipid metabolism and variants have been linked to Parkinson's disease (PD). Here, we find altered PSAP levels in the plasma, CSF and post-mortem brain of PD patients. Altered plasma and CSF PSAP levels correlatewith PD-relatedmotor impairments. Dopaminergic PSAP-deficient (cPSAP(DAT)) mice display hypolocomotion and depression/anxiety-like symptoms with mildly impaired dopaminergic neurotransmission, while serotonergic PSAP-deficient (cPSAP(SERT)) mice behave normally. Spatial lipidomics revealed an accumulation of highly unsaturated and shortened lipids and reduction of sphingolipids throughout the brains of cPSAP(DAT) mice. The overexpression of alpha-synuclein via AAV lead to more severe dopaminergic degeneration and higher p-Ser129 alpha-synuclein levels in cPSAP(DAT) mice compared to WT mice. Overexpression of PSAP via AAV and encapsulated cell biodelivery protected against 6-OHDA and alpha-synuclein toxicity in wild-type rodents. Thus, these findings suggest PSAP may maintain dopaminergic lipid homeostasis, which is dysregulated in PD, and counteract experimental parkinsonism.
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| 10. |
- Hulme, Heather, et al.
(författare)
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Simultaneous mass spectrometry imaging of multiple neuropeptides in the brain and alterations induced by experimental parkinsonism and L-DOPA therapy
- 2020
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Ingår i: Neurobiology of Disease. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0969-9961 .- 1095-953X. ; 137
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptides are important signalling molecules in the brain and alterations in their expression levels have been linked to neurological disorders such as Parkinson's disease. It is challenging to map neuropeptide changes across and within brain regions because of their low in vivo concentrations and complex post-translational processing. Consequently, the role of neuropeptides in Parkinson's disease is not well understood. Thus, we have developed and evaluated a method to image multiple neuropeptides simultaneously in both rat and primate brain tissue sections by matrix-assisted laser desorption/ionisation mass spectrometry imaging at high lateral resolution. Using a unilateral 6-hydroxydopamine rat model of Parkinson's disease, we imaged changes in enkephalins, dynorphins, tachykinins and neurotensin associated with the dopaminergic denervation and L-DOPA treatment in multiple brain regions. L-DOPA administration significantly affected neuropeptides in the globus pallidus, while neuropeptides in the caudate-putamen were mostly affected by dopamine depletion. Using high lateral resolution imaging, we observed an increase of neurotensin in the dorsal sub-region of the globus pallidus after dopamine depletion. This study highlights the capacity of mass spectrometry imaging to elucidate the dynamics of neuropeptide signalling during Parkinson's disease and its treatment.
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