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1.	Berg Hansen, Kristoffer, et al. (författare) Myocardial efficiency in patients with different aetiologies and stages of heart failure 2022 Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 23:3, s. 328-337 Tidskriftsartikel (refereegranskat)abstract Aims: Myocardial external efficiency (MEE) is the ratio of cardiac work in relation with energy expenditure. We studied MEE in patients with different aetiologies and stages of heart failure (HF) to discover the role and causes of deranged MEE. In addition, we explored the impact of patient characteristics such as sex, body mass index (BMI), and age on myocardial energetics.Methods and results: Cardiac energetic profiles were assessed with C-11-acetate positron emission tomography (PET) and left ventricular ejection fraction (LVEF) was acquired with echocardiography. MEE was studied in 121 participants: healthy controls (n = 20); HF patients with reduced (HFrEF; n = 25) and mildly reduced (HFmrEF; n = 23) LVEF; and patients with asymptomatic (AS-asymp; n = 38) and symptomatic (AS-symp; n = 15) aortic stenosis (AS). Reduced MEE coincided with symptoms of HF irrespective of aetiology and declined in tandem with deteriorating LVEF. Patients with AS-symp and HFmrEF had reduced MEE as compared with controls (22.2 +/- 4.9%, P = 0.041 and 20.0 +/- 4.2%, P < 0.001 vs. 26.1 +/- 5.8% in controls) and a further decline was observed in patients with HFrEF (14.7 +/- 6.3%, P < 0.001). Disproportionate left ventricular hypertrophy was a major cause of reduced MEE. Female sex (P < 0.001), a lower BMI (P = 0.001), and advanced age (P = 0.03) were associated with a lower MEE.Conclusion: MEE was reduced in patients with HFrEF, HFmrEF, and HF due to pressure overload and MEE may therefore constitute a treatment target in HF. Patients with LVH, advanced age, female sex, and low BMI had more pronounced reduction in MEE and personalized treatment within these patient subgroups could be relevant.
2.	Gregersen, Henrik, et al. (författare) Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma : A randomised phase 2 trial by the Nordic Myeloma Study Group 2022 Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 108:1, s. 34-44 Tidskriftsartikel (refereegranskat)abstract Objective We investigated the efficacy and safety of carfilzomib-containing induction before salvage high-dose melphalan with autologous stem-cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma. Methods This randomised, open-label, phase 2 trial included patients with first relapse of multiple myeloma after upfront ASCT who were re-induced with four cycles of carfilzomib, cyclophosphamide and dexamethasone. Two months after salvage, ASCT patients were randomised to either observation or maintenance therapy with iv carfilzomib 27 -> 56 mg/sqm and p.o. dexamethasone 20 mg every second week. The study enrolled 200 patients of which 168 were randomised to either maintenance with carfilzomib and dexamethasone (n = 82) or observation (n = 86). Results Median time to progression (TTP) after randomisation was 25.1 months (22.5-NR) in the carfilzomib-dexamethasone maintenance group and 16.7 months (14.4-21.8) in the control group (HR 0.46, 95% CI 0.30-0.71; P = .0004). The most common adverse events during maintenance were thrombocytopenia, anaemia, hypertension, dyspnoea and bacterial infections. Conclusion In summary, maintenance therapy with carfilzomib and dexamethasone after salvage ASCT prolonged TTP with 8 months. The maintenance treatment was in general well-tolerated with manageable toxicity.
3.	Hansson, Karl, 1985, et al. (författare) Corrigendum to "Use of the tau protein-to-peptide ratio in CSF to improve diagnostic classification of Alzheimer's disease" [Clin. Mass Spectrom. 14 (Part B) (2019) 74-82]. 2022 Ingår i: Journal of mass spectrometry and advances in the clinical lab. - : Elsevier BV. - 2667-145X. ; 26 Tidskriftsartikel (refereegranskat)abstract [This corrects the article DOI: 10.1016/j.clinms.2019.07.002.].
4.	Larsen, Anders Hostrup, et al. (författare) A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes 2020 Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:9, s. 1628-1637 Tidskriftsartikel (refereegranskat)abstract AimsThe present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin-resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes. Methods and resultsThirty-six HFrEF patients (ejection fraction 378%; median age 66years) were randomised to metformin (n = 19) or placebo (n = 17) for 3months in addition to standard heart failure therapy. The primary endpoint was change in myocardial efficiency expressed as the work metabolic index (WMI), assessed by C-11-acetate positron emission tomography and transthoracic echocardiography. Compared with placebo, metformin treatment (1450 +/- 550 mg/day) increased WMI [absolute mean difference, 1.0mmHg.mL.m(-2).10(6); 95% confidence interval (CI) 0.1 to 1.8; P = 0.03], equivalent to a 20% relative efficiency increase. Patients with above-median plasma metformin levels displayed greater WMI increase (25% vs. -4%; P = 0.02). Metformin reduced myocardial oxygen consumption (-1.6mL O-2.100 g(-1).min(-1); P = 0.014). Cardiac stroke work was preserved (-2J; 95% CI -11 to 7; P = 0.69). Metformin reduced body weight (-2.2kg; 95% CI -3.6 to -0.8; P = 0.003) and glycated haemoglobin levels (-0.2%; 95% CI -0.3 to 0.0; P = 0.02). Changes in resting and exercise ejection fraction, global longitudinal strain, and exercise capacity did not differ between groups. ConclusionMetformin treatment in non-diabetic HFrEF patients improved myocardial efficiency by reducing myocardial oxygen consumption. Measurement of circulating metformin levels differentiated responders from non-responders. These energy-sparing effects of metformin encourage further large-scale investigations in heart failure patients without diabetes.
5.	Loodin, Henrik, et al. (författare) Beteendeförändring, tag plats! 2021 Ingår i: Efter antibiotika : Om smitta i en ny tid - Om smitta i en ny tid. - 9789189139954 ; , s. 62-72 Bokkapitel (populärvet., debatt m.m.)
6.	Loodin, Henrik, et al. (författare) Beteendeförändring, tag plats!: : En undersökning av rum under förändring 2021 Ingår i: Att leva med bakterier : Möjligheter till ett levbart immunitärt liv - Möjligheter till ett levbart immunitärt liv. - 9789198439427 ; , s. 87-105 Bokkapitel (refereegranskat)
7.	Malmgren, Linnea, et al. (författare) The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation. 2023 Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 293:3, s. 293-308 Tidskriftsartikel (refereegranskat)abstract Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
8.	Moberg, Christina, et al. (författare) De unga gör helt rätt när de stämmer staten 2022 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)abstract 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
9.	Schmitz, Alexander, et al. (författare) Longitudinal minimal residual disease assessment in multiple myeloma patients in complete remission : results from the NMSG flow-MRD substudy within the EMN02/HO95 MM trial 2022 Ingår i: BMC Cancer. - : BMC. - 1471-2407. ; 22:1 Tidskriftsartikel (refereegranskat)abstract Background: Multiple myeloma remains an incurable disease with multiple relapses due to residual myeloma cells in the bone marrow of patients after therapy. Presence of small number of cancer cells in the body after cancer treatment, called minimal residual disease, has been shown to be prognostic for progression-free and overall survival. However, for multiple myeloma, it is unclear whether patients attaining minimal residual disease negativity may be candidates for treatment discontinuation. We investigated, if longitudinal flow cytometry-based monitoring of minimal residual disease (flow-MRD) may predict disease progression earlier and with higher sensitivity compared to biochemical assessments. Methods: Patients from the Nordic countries with newly diagnosed multiple myeloma enrolled in the European-Myeloma-Network-02/Hovon-95 (EMN02/HO95) trial and undergoing bone marrow aspiration confirmation of complete response, were eligible for this Nordic Myeloma Study Group (NMSG) substudy. Longitdudinal flow-MRD assessment of bone marrow samples was performed to identify and enumerate residual malignant plasma cells until observed clinical progression. Results: Minimal residual disease dynamics were compared to biochemically assessed changes in serum free light chain and M-component. Among 20 patients, reaching complete response or stringent complete response during the observation period, and with >= 3 sequential flow-MRD assessments analysed over time, increasing levels of minimal residual disease in the bone marrow were observed in six cases, preceding biochemically assessed disease and clinical progression by 5.5 months and 12.6 months (mean values), respectively. Mean malignant plasma cells doubling time for the six patients was 1.8 months (95% CI, 1.4-2.3 months). Minimal malignant plasma cells detection limit was 4 x 10-5. Conclusions: Flow-MRD is a sensitive method for longitudinal monitoring of minimal residual disease dynamics in multiple myeloma patients in complete response. Increasing minimal residual disease levels precedes biochemically assessed changes and is an early indicator of subsequent clinical progression.
10.	Wemrell, Maria, et al. (författare) Små socioekonomiska skillnader i antibiotikaanvändning i Sverige 2021 Ingår i: Efter antibiotika. Om smitta i en ny tid. - 9789189139954 Bokkapitel (populärvet., debatt m.m.)
11.	Abarkan, Abdellah, et al. (författare) Corona hotar förvärra svenska bostadskrisen. 108 forskare: Sveriges regering och kommuner måste förhindra en katastrof. 2020 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)abstract Debattartikel och Öppet brev publicerad i tidningen Aftonbladet. 29.3. 2020.
12.	Aguillon, David, et al. (författare) Plasma p-tau217 predicts in vivo brain pathology and cognition in autosomal dominant Alzheimer's disease 2023 Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:6, s. 2585-2594 Tidskriftsartikel (refereegranskat)abstract Introduction: Plasma-measured tau phosphorylated at threonine 217 (p-tau217) is a potential non-invasive biomarker of Alzheimer's disease (AD). We investigated whether plasma p-tau217 predicts subsequent cognition and positron emission tomography (PET) markers of pathology in autosomal dominant AD. Methods: We analyzed baseline levels of plasma p-tau217 and its associations with amyloid PET, tau PET, and word list delayed recall measured 7.61 years later in non-demented age- and education-matched presenilin-1 E280A carriers (n = 24) and non-carrier (n = 20) family members. Results: Carriers had higher plasma p-tau217 levels than non-carriers. Baseline plasma p-tau217 was associated with subsequent amyloid and tau PET pathology levels and cognitive function. Discussion: Our findings suggest that plasma p-tau217 predicts subsequent brain pathological burden and memory performance in presenilin-1 E280A carriers. These results provide support for plasma p-tau217 as a minimally invasive diagnostic and prognostic biomarker for AD, with potential utility in clinical practice and trials. Highlights: Non-demented presenilin-1 E280A carriers have higher plasma tau phosphorylated at threonine 217 (p-tau217) than do age-matched non-carriers. Higher baseline p-tau217 is associated with greater future amyloid positron emission tomography (PET) pathology burden. Higher baseline p-tau217 is associated with greater future tau PET pathology burden. Higher baseline p-tau217 is associated with worse future memory performance.
13.	Alamaa, Linda, et al. (författare) En infrastruktur för hållbar antibiotikaanvändning : Antibiotikaresistens som ett politiskt problem 2021 Ingår i: Att leva med bakterier: Möjligheter till ett levbart immunitärt liv. - 9789198439427 - 9789198439427 Bokkapitel (övrigt vetenskapligt/konstnärligt)
14.	Almeland, Stian, et al. (författare) The effect of microsurgical training on novice medical students’ basic surgical skills—a randomized controlled trial 2020 Ingår i: European journal of plastic surgery. - : Springer Science and Business Media LLC. - 0930-343X .- 1435-0130. ; 43, s. 459-466 Tidskriftsartikel (refereegranskat)abstract Background It has been demonstrated that medical students are capable of learning microsurgical techniques. We hypothesize that microsurgical training might give insight into the importance of delicate tissue handling and correct knot tying that could have a positive influence on macrosurgical skills. The primary aim of this study was to evaluate the effect of microsurgical training on macrosurgical suturing skills in novice medical students. Subjects and methods In 2018, 46 novice medical students were enrolled and randomized into two groups. The intervention group received both macro- and microsurgical training and the control group received only microsurgical training. Both groups underwent an assessment test that consisted of macrosurgical tasks of three simple interrupted sutures with a square knot and continuous three-stitch long over-and-over sutures. These tests were individually filmed and assessed using the University of Bergen suturing skills assessment tool (UBAT) and the Objective Structured Assessment of Technical Skill global rating scale (OSATS). Questionnaires regarding future career ambitions and attitudes towards plastic surgery were also completed both prior to and following the tests. Results The intervention group needed a longer time to complete the tasks than the control group (12.2 min vs. 9.6 min, p>0.001), and scored lower on both the UBAT (5.6 vs. 9.0, p>0.001) and the OSATS (11.1 vs. 13.1, p>0.001) assessments. The microsurgery course tended to positively influence the students’ attitudes towards a career in plastic surgery (p=0.002). This study demonstrates poorer macrosurgical skills in the medical students group exposed to microsurgical training. The true effect of microsurgical training warrants further investigation.
15.	Andersson, Emelie, et al. (författare) Blood and cerebrospinal fluid neurofilament light differentially detect neurodegeneration in early Alzheimer's disease 2020 Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 95, s. 143-153 Tidskriftsartikel (refereegranskat)abstract Cerebrospinal fluid (CSF) neurofilament light (NfL) concentration has reproducibly been shown to reflect neurodegeneration in brain disorders, including Alzheimer's disease (AD). NfL concentration in blood correlates with the corresponding CSF levels, but few studies have directly compared the reliability of these 2 markers in sporadic AD. Herein, we measured plasma and CSF concentrations of NfL in 478 cognitively unimpaired (CU) subjects, 227 patients with mild cognitive impairment, and 113 patients with AD dementia. We found that the concentration of NfL in CSF, but not in plasma, was increased in response to Aβ pathology in CU subjects. Both CSF and plasma NfL concentrations were increased in patients with mild cognitive impairment and AD dementia. Furthermore, only NfL in CSF was associated with reduced white matter microstructure in CU subjects. Finally, in a transgenic mouse model of AD, CSF NfL increased before serum NfL in response to the development of Aβ pathology. In conclusion, NfL in CSF may be a more reliable biomarker of neurodegeneration than NfL in blood in preclinical sporadic AD.
16.	Andersson, E., et al. (författare) Cerebral A beta deposition precedes reduced cerebrospinal fluid and serum A beta 42/A beta 40 ratios in the App(NL-F/NL-F) knock-in mouse model of Alzheimer's disease 2023 Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 15:1 Tidskriftsartikel (refereegranskat)abstract BackgroundA beta 42/A beta 40 ratios in cerebrospinal fluid (CSF) and blood are reduced in preclinical Alzheimer's disease (AD), but their temporal and correlative relationship with cerebral A beta pathology at this early disease stage is not well understood. In the present study, we aim to investigate such relationships using App knock-in mouse models of preclinical AD.MethodsCSF, serum, and brain tissue were collected from 3- to 18-month-old App(NL-F/NL-F) knock-in mice (n = 48) and 2-18-month-old App(NL/NL) knock-in mice (n = 35). The concentrations of A beta 42 and A beta 40 in CSF and serum were measured using Single molecule array (Simoa) immunoassays. Cerebral A beta plaque burden was assessed in brain tissue sections by immunohistochemistry and thioflavin S staining. Furthermore, the concentrations of A beta 42 in soluble and insoluble fractions prepared from cortical tissue homogenates were measured using an electrochemiluminescence immunoassay.ResultsIn App(NL-F/NL-F) knock-in mice, A beta 42/A beta 40 ratios in CSF and serum were significantly reduced from 12 and 16 months of age, respectively. The initial reduction of these biomarkers coincided with cerebral A beta pathology, in which a more widespread A beta plaque burden and increased levels of A beta 42 in the brain were observed from approximately 12 months of age. Accordingly, in the whole study population, A beta 42/A beta 40 ratios in CSF and serum showed a negative hyperbolic association with cerebral A beta plaque burden as well as the levels of both soluble and insoluble A beta 42 in the brain. These associations tended to be stronger for the measures in CSF compared with serum. In contrast, no alterations in the investigated fluid biomarkers or apparent cerebral A beta plaque pathology were found in App(NL/NL) knock-in mice during the observation time.ConclusionsOur findings suggest a temporal sequence of events in App(NL-F/NL-F) knock-in mice, in which initial deposition of A beta aggregates in the brain is followed by a decline of the A beta 42/A beta 40 ratio in CSF and serum once the cerebral A beta pathology becomes significant. Our results also indicate that the investigated biomarkers were somewhat more strongly associated with measures of cerebral A beta pathology when assessed in CSF compared with serum.
17.	Andersson, Emelie, et al. (författare) Cerebral Aβ deposition precedes reduced cerebrospinal fluid and serum Aβ42/Aβ40 ratios in the App NL−F/NL−F knock-in mouse model of Alzheimer’s disease 2023 Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 15:1 Tidskriftsartikel (refereegranskat)abstract Background: Aβ42/Aβ40 ratios in cerebrospinal fluid (CSF) and blood are reduced in preclinical Alzheimer’s disease (AD), but their temporal and correlative relationship with cerebral Aβ pathology at this early disease stage is not well understood. In the present study, we aim to investigate such relationships using App knock-in mouse models of preclinical AD. Methods: CSF, serum, and brain tissue were collected from 3- to 18-month-old AppNL−F/NL−F knock-in mice (n = 48) and 2–18-month-old AppNL/NL knock-in mice (n = 35). The concentrations of Aβ42 and Aβ40 in CSF and serum were measured using Single molecule array (Simoa) immunoassays. Cerebral Aβ plaque burden was assessed in brain tissue sections by immunohistochemistry and thioflavin S staining. Furthermore, the concentrations of Aβ42 in soluble and insoluble fractions prepared from cortical tissue homogenates were measured using an electrochemiluminescence immunoassay. Results: In AppNL−F/NL−F knock-in mice, Aβ42/Aβ40 ratios in CSF and serum were significantly reduced from 12 and 16 months of age, respectively. The initial reduction of these biomarkers coincided with cerebral Aβ pathology, in which a more widespread Aβ plaque burden and increased levels of Aβ42 in the brain were observed from approximately 12 months of age. Accordingly, in the whole study population, Aβ42/Aβ40 ratios in CSF and serum showed a negative hyperbolic association with cerebral Aβ plaque burden as well as the levels of both soluble and insoluble Aβ42 in the brain. These associations tended to be stronger for the measures in CSF compared with serum. In contrast, no alterations in the investigated fluid biomarkers or apparent cerebral Aβ plaque pathology were found in AppNL/NL knock-in mice during the observation time. Conclusions: Our findings suggest a temporal sequence of events in AppNL−F/NL−F knock-in mice, in which initial deposition of Aβ aggregates in the brain is followed by a decline of the Aβ42/Aβ40 ratio in CSF and serum once the cerebral Aβ pathology becomes significant. Our results also indicate that the investigated biomarkers were somewhat more strongly associated with measures of cerebral Aβ pathology when assessed in CSF compared with serum.
18.	Andersson, Emelie, et al. (författare) CSF Aβ42 and Aβ40 and their relation to brain soluble and insoluble Aβ in the 5xFAD mouse model of Alzheimer's disease 2021 Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279. ; 17 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: In patients with AD, CSF Aβ42 is reduced while Aβ40 remains unchanged. It has been suggested that altered CSF Aβ42 is due to aggregation of this peptide into insoluble plaques, resulting in less soluble Aβ42 available for secretion to the CSF. However, the relations between soluble and insoluble Aβ42 and Aβ40 in the brain and the concentrations of these Aβ peptides in CSF are not well studied. METHODS: CSF and cortical brain tissue was collected from 2, 4, 6, and 12 months old male and female 5xFAD mice (n=45). CSF Aβ42 and Aβ40 concentrations were measured using Single molecule array (Simoa) technology. Brain sections were prepared and immunohistochemically (IHC) stained using antibodies specific for Aβ42 and Aβ40. The concentrations of Aβ42 and Aβ40 in soluble (extracted with TBS) and insoluble (extracted with formic acid) cortical brain fractions were determined by the Meso Scale Discovery technique. RESULTS: CSF Aβ42 was decreased over time whereas CSF Aβ40 remained unaltered (Fig 1). In the same mice, IHC revealed an age-related increased deposition of both Aβ42 and Aβ40 in insoluble plaques from 2 months of age (Fig 2). Moreover, measurements of Aβ42 and Aβ40 in soluble and insoluble cortical brain fractions showed increased concentrations of both peptides over time (Fig 3). CSF Aβ42 correlated inversely with cortical deposition of Aβ42 determined with IHC and the concentrations of Aβ42 in soluble and insoluble brain fractions. In contrast, no such correlations were found for Aβ40 (Fig 4). Although cortical levels of the two Aβ peptides were higher in females than in males, these sex differences were not reflected in CSF (Fig 5). CONCLUSIONS: Although significant depositions of both Aβ42 and Aβ40 were found in the brain, only Aβ42 was altered in CSF. Together with the finding that Aβ42 was increased, and not reduced, in soluble cortical brain fractions, this may suggest that mechanisms other than aggregation of Aβ42 into insoluble plaques contribute to decreased CSF concentrations of this Aβ peptide in 5xFAD mice. However, additional characterization of Aβ in the soluble brain fraction is needed to further understand its relation to the concentrations in CSF.
19.	Ashton, Nicholas J., et al. (författare) A multicentre validation study of the diagnostic value of plasma neurofilament light 2021 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-12 Tidskriftsartikel (refereegranskat)abstract Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
20.	Ashton, Nicholas J., et al. (författare) Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer's trial selection and disease monitoring. 2022 Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 28:12, s. 2555-2562 Tidskriftsartikel (refereegranskat)abstract Blood biomarkers indicative of Alzheimer's disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40 ratio were more changed at lower thresholds of amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4-6years in both preclinical and symptomatic stages of the disease, with no such changes observed in p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein or neurofilament light. Only longitudinal increases of p-tau217 were also associated with clinical deterioration and brain atrophy in preclinical AD. The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer's Prevention). These findings support the differential association of plasma biomarkers with disease development and strongly highlight p-tau217 as a surrogate marker of disease progression in preclinical and prodromal AD, with impact for the development of new disease-modifying treatments.
21.	Ashton, Nicholas J., et al. (författare) The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers 2021 Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48, s. 2140-2156 Tidskriftsartikel (refereegranskat)abstract Purpose The development of blood biomarkers that reflect Alzheimer's disease (AD) pathophysiology (phosphorylated tau and amyloid-beta) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomarkers. Methods A panel of experts convened in November 2019 at a two-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of blood biomarkers was assessed based on the Biomarker Roadmap methodology and discussed fully during the workshop which also evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. Results Plasma p-tau has shown analytical validity (phase 2 primary aim 1) and first evidence of clinical validity (phase 3 primary aim 1), whereas the maturity level for A beta remains to be partially achieved. Full and partial achievement has been assigned to p-tau and A beta, respectively, in their associations to ante-mortem measures (phase 2 secondary aim 2). However, only preliminary evidence exists for the influence of covariates, assay comparison and cut-off criteria. Conclusions Despite the relative infancy of blood biomarkers, in comparison to CSF biomarkers, much has already been achieved for phases 1 through 3 - with p-tau having greater success in detecting AD and predicting disease progression. However, sufficient data about the effect of covariates on the biomarker measurement is lacking. No phase 4 (real-world performance) or phase 5 (assessment of impact/cost) aim has been tested, thus not achieved.
22.	Att leva med bakterier : Möjligheter till ett levbart immunitärt liv 2021 Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract Att leva med bakterier: möjligheter till ett levbart immunitärt liv är en antologi som tvärvetenskapligt undersöker betydelsen av bakteriers växande antibiotikaresistens. Detta är en förändring som håller på att göra antibiotikan ineffektiv och därmed omskapa den mänskliga historien på lång sikt. Det uppskattas att tio miljoner människor år 2050 kommer att dö av infektioner som inte längre svarar på den i dag tillgängliga antibiotikan. Hur kan vi här och nu hitta alternativa vägar mot en mer levbar framtid – med eller utan verksam antibiotika? Antologin är ett resultat av det tvärvetenskapliga forskarsamarbete som under 2019-20 bedrevs vid Pufendorfinstitutet, Lunds universitetet under Temat Postantibiotiska framtider. I antologin utvecklar tio forskare sina tankar och idéer kring hur samhället idag och i morgon kan utformas för att hantera smittämnen som bakterier och virus i vår vardag. Smittämnen det i framtiden kanske inte finns något botemedel mot.
23.	Barbu, Mikael, et al. (författare) Dextran- versus crystalloid-based prime in cardiac surgery: A prospective randomized pilot study. 2020 Ingår i: The Annals of thoracic surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 110:5, s. 1541-7 Tidskriftsartikel (refereegranskat)abstract The optimum priming fluid for the cardiopulmonary bypass (CPB) circuit is still debated. We compared a new hyperoncotic priming solution containing dextran 40, which has an electrolyte composition that mimics extracellular fluid, with a standard crystalloid-based prime.Eighty cardiac surgery patients were included in this double-blind randomized single-centre study. The patients were randomized to either a dextran-based prime or a crystalloid prime containing Ringer acetate and mannitol. The primary endpoint was colloid oncotic pressure (COP) in serum during CPB. Secondary endpoints included fluid balance, bleeding and transfusion requirements, pulmonary function, hemolysis, systemic inflammation, and markers of renal, hepatic, myocardial, and brain injury. Blood samples were collected before, during, and after CPB.COP was higher in the dextran group than in the crystalloid prime group on CPB (18.8±2.9 vs. 16.4±2.9 mmHg, p<0.001) and 10 min after CPB (19.2±2.7 vs. 16.8±2.9 mmHg, p<0.001). Patients in the dextran group required less intravenous fluid during CPB (1090±499 vs. 1437±543 ml; p=0.003) and net fluid balance was less positive 12h after surgery (+1,431±741 vs. +1,901±922 ml; p=0.014). Plasma free hemoglobin was significantly lower in the dextran group 2h after CPB (0.18±0.11 vs 0.41±0.33, p=0.001). There were no significant differences in bleeding, transfusion requirements, organ function, systemic inflammation, or brain and myocardial injury markers between the groups at any time point.Our results suggest that a hyperoncotic dextran-based priming solution preserves intraoperative COP compared to crystalloid prime. Larger studies with clinically valid endpoints are necessary to evaluate hyperoncotic prime solutions further.
24.	Berg, Charlotte, et al. (författare) Utegående nötkreatur och får 2020 Rapport (övrigt vetenskapligt/konstnärligt)
25.	Berg, Lotta, et al. (författare) Digital tillsynsteknik i djurhållning utomhus 2020 Rapport (övrigt vetenskapligt/konstnärligt)abstract I enlighet med Jordbruksverkets förfrågan behandlar denna rapport tre områden för digital teknik vid övervakning och kontroll av djur som vistas utomhus på stora ytor: (1) kamerateknologi, t.ex. användning av drönare, (2) positioneringsteknologi som GPS och (3) teknologi för att styra djurens rörelser, som drivning med drönare och användning av s.k. virtuella stängsel. De tre teknikområdena överlappar delvis varandra. Digital tillsyn av utegående djur är beroende av att sensorer mäter det man tror att de mäter med tillräcklig noggrannhet och att data kan överföras och bearbetas till information som lagras och analyseras på ett säkert och korrekt sätt. Sådana teknologier benämns med samlingsnamnet ’Precision Livestock Farming’ (PLF). Användningen av informationen är avgörande för teknikens användbarhet i tillsyns- och djurskyddsarbete. Tillämpningarna är till viss del reglerade av gällande lagstiftning, exempelvis genom krav på tillsyn, begränsad användning av elektricitet för att styra djurs beteende, användning av obemannade luftfarkoster, d.v.s. drönare, samt åtgärder för att förhindra att utrustning skadar djuren eller påverkar deras hälsa och beteende. Inom PLF används en rad olika sensorer som direkt eller indirekt kan mäta djurens miljö och djurens beteende och fysiologiska tillstånd. Den teknologiska utvecklingen har främst varit inriktad på mjölkkor, fjäderfän och grisar och endast i liten utsträckning berört häst, får och get. För djur på bete är överföringen av data från en enhet på eller vid djuret till en mottagare särskilt problematisk p.g.a. stora avstånd, men det sker en snabb teknisk utveckling mot effektivare överföring. PLF-teknologin innebär i de flesta fall att djuren övervakas kontinuerligt och att avvikelser i t.ex. deras hälsotillstånd och välfärd i princip kan upptäckas i realtid, vilket ska ställas mot nuvarande lagkrav på tillsyn minst en eller två gånger dagligen. Sensorer kan ge information om ett stort antal fysiologiska tillstånd och beteenden. En av de vanligaste teknikerna är sensorer för aktivitet. Indirekt kan de också ge information om idissling, liggtid, stegantal och ättid och utlösa larm om exempelvis brunst, hälsoproblem, hälta och kalvning. Sensorer kan även placeras i förmagen hos idisslare (s.k. våmbolus) där de mäter våm-pH och kan larma om störningar i magfunktionen, eller utformas som termometrar som kan larma om hälsostörningar, kalvning och vattenintag eller mikrofoner som kan mäta idissling och larma om brunst, kalvning och onormalt idisslingsmönster. Med kamerateknik kan man mäta aktivitet, kroppsform och hudtemperatur, vilket kan ge information om ketosstatus, hull, hälta och juverhälsa. Kameror monterade på drönare kan användas för att lokalisera och räkna djur, bestämma deras position, habitatval och till viss del deras beteende, särskilt när djuren rör sig över stora arealer. Det finns flera elektroniska positioneringsteknologier varav passiv ’Radio Frequency Identification RFID’ är den vanligaste. Räckvidden är kort med denna teknik men den kan vara användbar om man t.ex. vill mäta hur ofta djuren besöker en vattenpost. Andra teknologier kan med hjälp av antenner följa djurens positioner i realtid. GPS-enheter monterade i halsband kan regelbundet registrera djurens geografiska position. Användningen av GPS har blivit relativt vanlig i renskötseln vilket tycks ha lett till en förbättrad arbetssituation för renskötarna. Positionering med GPS ger inte alltid exakta uppgifter men tekniken har visat sig användbar för studier av habitatval, sociala interaktioner och gruppdynamik. Med positionerna från GPS har man också kunnat styra djur till områden med bättre betestillgång. Med en tillräckligt frekvent bestämning av position med hjälp av GPS (ca en gång per minut) är det möjligt att bestämma betestiden för nötkreatur på ett tillförlitligt sätt. En användning av drönare i djurskötsel och djurtillsyn kan vara att med hjälp av kamera lokalisera djuren över stora ytor. Denna användning begränsas dock av nuvarande bestämmelser om att föraren måste ha ögontakt med drönaren. I renskötseln har drönare börjat användas för att förflytta djur men denna tillämpning är ännu inte juridiskt reglerad. Virtuella stängsel är strukturer som bestäms med kartkoordinater eller elektronisk sändare på marken. Stängslen fungerar som inhägnader, hinder eller gränser. Djuren mottar signaler (vanligen ljud) och stimuli (vanligen elstötar från ett halsband) som gör det möjligt för dem att lära sig var stängslet finns. I vetenskapliga studier har man med varierande framgång lyckats lära djuren att associera ljudsignaler och elstötar med en gräns som inte får passeras. Förmågan att lära sig skiljer mellan olika djurslag, liksom mellan individer. Det finns fortfarande många obesvarade frågeställningar om hur djur kan anpassa sig till virtuella stängselsystemet, liksom hur de påverkas, både under inlärningsfas och bruksfas.
26.	Berg, Lotta, et al. (författare) Hållande av hund och katt : Behov av social kontakt och fysisk aktivitet, samt lämplig ålder för avvänjning 2020 Rapport (övrigt vetenskapligt/konstnärligt)
27.	Berg, Lotta, et al. (författare) Minkhållning i Sverige 2020 Rapport (övrigt vetenskapligt/konstnärligt)abstract Den här rapporten är framtagen av SLUs vetenskapliga råd för djurskydd i syfte att utvärdera djurvälfärden hos minkar inom svensk pälsdjursproduktion och bedöma om den vetenskapliga litteraturen ger stöd för att produktionen, så som den bedrivs i dag, ger djuren möjlighet att bete sig naturligt. Minkar som föds upp för pälsproduktion i Sverige måste hållas och skötas enligt Statens jordbruksverks föreskrifter och allmänna råd (SJVFS 2012:14) om uppfödning och hållande av pälsdjur. Rapporten har tagits fram på uppdrag av Jordbruksverket som en del i ett regeringsuppdrag om minkhållning. Den beskriver minkens ursprung och domesticering, naturligt beteende hos vild mink, inhysning och skötsel vid pälsuppfödning, onormalt beteende, miljöberikningar, smittskydd, förekommande sjukdomar och avlivningsmetoder. I rapporten ges rekommendationer baserat på tillgänglig vetenskaplig litteratur, och behov av framtida forskning identifieras.Minken är en opportunistisk köttätare som behöver äta relativt ofta. I pälsdjursproduktionen tillämpas i princip fri tillgång på foder till digivande honor och växande valpar men inför parningssäsongen innebär den fria tillgången ökad risk för komplikationer vid valpningen på grund av övervikt hos honan. Fodringen behöver därför anpassas under vintern för att minska risken för feta honor och därmed ökad dödlighet vid valpningen. Neddragen fodertillgång kan orsaka frustration som då visar sig i beteendestörningar. Olika aspekter på utfodring bör därför beaktas i framtida forskning. Den vilda minken lever solitärt under stora delar av året, dock kan en till flera honor leva inom en hanes revir. I pälsdjursproduktionen bör därför vuxna minkar hållas individuellt, undantaget är växande ungminkar som med fördel kan hållas tillsammans. Att hålla två minkar tillsammans är det vanligaste, dock fungerar det att hålla tre ungminkar i etagebur om de ges extra foder och god tillsyn. Grupper med fler än tre djur bör undvikas då riskerna för aggression ökar. En lya fastsatt utanpå buren är viktigt för alla minkar året runt då de naturligt vilar mycket i sina bohål, samt även för att minkhonan ska kunna ta hand om de outvecklade ungarna första tiden efter födelsen. I fångenskap används halm för att skapa ett varmt bo under den kalla årstiden samt för att bygga ett bo för ungarna under uppfödningsperioden.Systematisk genetisk selektion för önskat beteende (temperament) förbättrar välfärden hos minken. Systemet tillämpas på svenska gårdar genom att minkar som uppvisar rädsla eller stress selekteras bort vid avelsurvalet. Urvalet av avelsdjur görs kontinuerligt från det att valparna föds, då reproduktion, valpöverlevnad och temperament registreras tidigt och är viktiga parametrar att ta hänsyn till i urvalet. Det slutliga urvalen sker på hösten då längd, vikt och pälsegenskaper graderas. Ju tidigare dessa urval görs desto tidigare kan utfodringen anpassas för att undvika att avelsdjuren blir överviktiga under hösten. Det är viktigt att aveln inte resulterar i för stora djur, då detta kan leda till välfärdsproblem i framtiden.Mink i vilt tillstånd använder vatten i sin jakt på bytesdjur, men är inget vattenlevande djur, per se. Badvatten till mink bedöms däremot vara en positiv berikning, dock inte vetenskapligt belagt, som ett grundläggande beteendebehov. Forskning visar att beteendestörningar kan förebyggas genom att minkarna ges fri tillgång på foder, hålls i etageburar med bolåda, hyllor, strömedel och berikningar som byts ut regelbundet. I svenska djurskyddsföreskrifter ingår dessa som krav för hållande av mink för pälsdjursproduktion. Mer kunskap behövs för hur ofta berikningar bör skiftas.Djurvälfärd i samband med livdjurstransport och avlivning av mink lyfts fram som angelägna forskningsområden. En snabb avlivning vid hemmaburen bedöms vara det bästa ur djurvälfärdssynpunkt. För att minska risken för spridning av sjukdomar bör importerade minkar hållas i karantän och hög biosäkerhet tillämpas på gården.
28.	Bergman, Lina, 1982, et al. (författare) Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT): a study protocol for a Swedish prospective multicentre cohort study 2020 Ingår i: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 10:9, s. e033851-e033851 Tidskriftsartikel (refereegranskat)abstract Introduction First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples. Methods and analysis This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications. Ethics and dissemination Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed journals.
29.	Bjursten, Henrik, et al. (författare) Once after a full moon : acute type A aortic dissection and lunar phases 2022 Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press. - 1569-9293 .- 1569-9285. ; 34:1, s. 105-110 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD.METHODS: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period).RESULTS: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00-1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01-1.23, P = 0.027). The peak incidence came 4-6 days after the moon was fully illuminated.CONCLUSIONS: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable.
30.	Bjurström, Martin F., et al. (författare) Central nervous system monoaminergic activity in hip osteoarthritis patients with disabling pain : associations with pain severity and central sensitization 2022 Ingår i: Pain Reports. - 2471-2531. ; 7:1, s. 988-988 Tidskriftsartikel (refereegranskat)abstract Introduction: Monoaminergic activity modulates nociceptive transmission in the central nervous system (CNS). Although pain is the most disabling symptom of osteoarthritis (OA), limited knowledge exists regarding the CNS mechanisms that amplify pain and drive sensitization processes in humans.Objectives:The main objective of this study was to evaluate associations between cerebrospinal fluid (CSF) monoamine metabolites, pain severity, and central sensitization in patients with OA undergoing total hip arthroplasty (THA).Methods:Patients with OA (n = 52) and pain-free controls (n = 30) provided CSF samples for measurement of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), noradrenaline (3-methoxy-4-hydroxyphenylglycol [HMPG]), and dopamine (homovanillic acid [HVA]) monoamine metabolites. Patients with OA completed longitudinal evaluation of pain using clinical measures and quantitative sensory testing.Results:Patients with OA had higher HMPG levels when compared with controls (P = 0.036). Within patients with OA undergoing THA, higher 5-HIAA and HVA levels were consistently associated with higher preoperative pain severity. Higher concentrations of 5-HIAA and HVA were also associated with lower conditioned pain modulation levels, whereas higher HMPG levels were linked to more efficient conditioned pain modulation. Patients with higher levels of CSF HVA exhibited increased pressure pain sensitivity (arm pressure pain detection threshold < 250 kPa vs ≥ 250 kPa, P = 0.042). Higher preoperative levels of CSF 5-HIAA predicted poorer pain control 6 months postoperatively (brief pain inventory pain severity; adjusted β = 0.010, 95% CI 0.001-0.019).Conclusions:In OA patients with disabling pain, higher CSF levels of serotonin and dopamine metabolites are associated with increased pain severity and central sensitization. Increased noradrenergic activity may be associated with more efficient pain inhibitory capacity.
31.	Blennow, Kaj, et al. (författare) Cerebrospinal fluid tau fragment correlates with tau PET : a candidate biomarker for tangle pathology 2020 Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 143:2, s. 650-660 Tidskriftsartikel (refereegranskat)abstract To date, there is no validated fluid biomarker for tau pathology in Alzheimer's disease, with contradictory results from studies evaluating the correlation between phosphorylated tau in CSF with tau PET imaging. Tau protein is subjected to proteolytic processing into fragments before being secreted to the CSF. A recent study suggested that tau cleavage after amino acid 368 by asparagine endopeptidase (AEP) is upregulated in Alzheimer's disease. We used immunoprecipitation followed by mass spectrometric analyses to evaluate the presence of tau368 species in CSF. A novel Simoa® assay for quantification of tau368 in CSF was developed, while total tau (t-tau) was measured by ELISA and the presence of tau368 in tangles was evaluated using immunohistochemistry. The diagnostic utility of tau368 was first evaluated in a pilot study (Alzheimer's disease = 20, control = 20), then in a second cohort where the IWG-2 biomarker criteria were applied (Alzheimer's disease = 37, control = 45), and finally in a third cohort where the correlation with 18F-GTP1 tau PET was evaluated (Alzheimer's disease = 38, control = 11). The tau368/t-tau ratio was significantly decreased in Alzheimer's disease (P < 0.001) in all cohorts. Immunohistochemical staining demonstrated that tau fragments ending at 368 are present in tangles. There was a strong negative correlation between the CSF tau368/t-tau ratio and 18F-GTP1 retention. Our data suggest that tau368 is a tangle-enriched fragment and that the CSF ratio tau368/t-tau reflects tangle pathology. This novel tau biomarker could be used to improve diagnosis of Alzheimer's disease and to facilitate the development of drug candidates targeting tau pathology. Furthermore, future longitudinal studies will increase our understanding of tau pathophysiology in Alzheimer's disease and other tauopathies.
32.	Blennow, Kaj, 1958, et al. (författare) Second-generation Elecsys cerebrospinal fluid immunoassays aid diagnosis of early Alzheimer's disease. 2023 Ingår i: Clinical chemistry and laboratory medicine. - : Walter de Gruyter GmbH. - 1437-4331 .- 1434-6621. ; 61:2, s. 234-244 Tidskriftsartikel (refereegranskat)abstract Timely diagnosis of Alzheimer's disease (AD) is critical for appropriate treatment/patient management. Cerebrospinal fluid (CSF) biomarker analysis is often used to aid diagnosis. We assessed analytical performance of second-generation (Gen II) Elecsys® CSF immunoassays (Roche Diagnostics International Ltd), and adjusted existing cut-offs, to evaluate their potential utility in clinical routine.Analytical performance was assessed using CSF samples measured with Elecsys CSF Gen II immunoassays on cobas e analyzers. Aβ42 Gen I/Gen II immunoassay method comparisons were performed (Passing-Bablok regression). Cut-off values were adjusted using estimated bias in biomarker levels between BioFINDER protocol aliquots/Gen I immunoassays and Gen II protocol aliquots/immunoassays. Distribution of Gen II immunoassay values was evaluated in AD, mild cognitive impairment (MCI), and cognitively normal cohorts; percentage observations outside the measuring range were derived.The Gen II immunoassays demonstrated good analytical performance, including repeatability, intermediate precision, lot-to-lot agreement (Pearson's r:≥0.999), and platform agreement (Pearson's r:≥0.995). Aβ42 Gen I/Gen II immunoassay measurements were strongly correlated (Pearson's r: 0.985-0.999). Aβ42 Gen II immunoassay cut-offs were adjusted to 1,030 and 800ng/L, and pTau181/Aβ42 ratio cut-offs to 0.023 and 0.029, for Gen II and I protocols, respectively. No observations were below the lower limit of the measuring range; above the upper limit, there were none from the AD cohort, and 2.6 and 6.8% from the MCI and cognitively normal cohorts, respectively.Our findings suggest that the Gen II immunoassays have potential utility in clinical routine to aid diagnosis of AD.
33.	Bogdanovic, Nenad, et al. (författare) [Alzheimer's disease - the most common cause of dementia]. : Alzheimers sjukdom – diagnostik och behandling i dag och i framtiden. 2020 Ingår i: Lakartidningen. - 1652-7518. ; 117 Tidskriftsartikel (refereegranskat)abstract Alzheimer's disease is the most common cause of dementia. As many as 250,000 people in Sweden will have a dementia disease in 2050. The »amyloid cascade hypothesis« is a common model which explains how β-amyloid affects the function of the nerve cells. Alzheimer's disease has a long-lasting course and can present in typical and atypical forms. CSF analyses for »core AD CSF biomarkers« and synaptic proteins have been available for clinical diagnostics. PET scanning can detect either β-amyloid or tau aggregates in the brain of living humans. Current Alzheimer's disease therapy is based on two classes of cognition-enhancing drugs: acetylcholinesterase inhibitor and NMDA-receptor antagonist, which delays cognitive decline in most patients. The latest clinical development of potential therapy for Alzheimer's is active or passive immunotherapy against brain β-amyloid and tau, where several studies have shown varying but promising treatment effects. Non-pharmacological interventions in patients with AD aim to delay the loss of mental abilities, helping people to be independent in everyday life for as long as possible, and to increase their well-being and quality of life.
34.	Bogdanovic, Nenad, et al. (författare) Alzheimers sjukdom – diagnostik och behandling i dag och i framtiden 2020 Ingår i: Läkartidningen. - 0023-7205. ; 117 Tidskriftsartikel (refereegranskat)abstract Alzheimer's disease is the most common cause of dementia. As many as 250,000 people in Sweden will have a dementia disease in 2050. The »amyloid cascade hypothesis« is a common model which explains how β-amyloid affects the function of the nerve cells. Alzheimer's disease has a long-lasting course and can present in typical and atypical forms. CSF analyses for »core AD CSF biomarkers« and synaptic proteins have been available for clinical diagnostics. PET scanning can detect either β-amyloid or tau aggregates in the brain of living humans. Current Alzheimer's disease therapy is based on two classes of cognition-enhancing drugs: acetylcholinesterase inhibitor and NMDA-receptor antagonist, which delays cognitive decline in most patients. The latest clinical development of potential therapy for Alzheimer's is active or passive immunotherapy against brain β-amyloid and tau, where several studies have shown varying but promising treatment effects. Non-pharmacological interventions in patients with AD aim to delay the loss of mental abilities, helping people to be independent in everyday life for as long as possible, and to increase their well-being and quality of life.
35.	Boscolo Bibi, Sara, 1993- (författare) Going for gold : A spectroelectrochemical and catalytic study of gold materials 2023 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract With the increase in demand for renewable energy, understanding chemical processes is essential for improving the design of catalysts in order to achieve better performance. This thesis summarises the experimental investigation of three types of catalytic gold materials: gold oxide formed from gold films, oxide-derived gold (OD-Au) produced from gold films, and gold nanoparticles supported on metal oxides. Different spectroscopic techniques were employed, such as operando sum frequency generation (SFG) and in situ and ex situ X-ray spectroscopies. These methods allowed the probing of the electronic and chemical states of gold after oxidising electrochemical treatments. The results indicate the presence of subsurface gold oxide remnants after formation of OD-Au, which may help explain its improved catalytic properties with respect to pure gold. In addition, a mathematical model to couple the early stages of gold oxide formation with the nonlinear optical response of gold during this process is presented. This model suggests that the growth proceeds from small oxide islands to 3D oxide growth, while SFG oxidation variation is due to the suppression of the free electron density by negatively-charged adsorbing oxygen atoms. Gold oxide was also studied with both in situ and operando X-ray spectroscopies, showing the importance of a continuous electrochemical treatment during measurements to avoid beam induced effects. Furthermore, gold nanoparticles supported on metal oxides (TiO2 and γ-Fe2O3) were investigated mainly with mass spectrometry. The results indicate two different reaction pathways for oxidation of CO to CO2 depending on the type of metal oxide support. These findings could be used to help design future gold-based catalysts.
36.	Brand, Abby L., et al. (författare) The performance of plasma amyloid beta measurements in identifying amyloid plaques in Alzheimer's disease : a literature review 2022 Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1, s. 195-195 Forskningsöversikt (refereegranskat)abstract The extracellular buildup of amyloid beta (Aβ) plaques in the brain is a hallmark of Alzheimer's disease (AD). Detection of Aβ pathology is essential for AD diagnosis and for identifying and recruiting research participants for clinical trials evaluating disease-modifying therapies. Currently, AD diagnoses are usually made by clinical assessments, although detection of AD pathology with positron emission tomography (PET) scans or cerebrospinal fluid (CSF) analysis can be used by specialty clinics. These measures of Aβ aggregation, e.g. plaques, protofibrils, and oligomers, are medically invasive and often only available at specialized medical centers or not covered by medical insurance, and PET scans are costly. Therefore, a major goal in recent years has been to identify blood-based biomarkers that can accurately detect AD pathology with cost-effective, minimally invasive procedures.To assess the performance of plasma Aβ assays in predicting amyloid burden in the central nervous system (CNS), this review compares twenty-one different manuscripts that used measurements of 42 and 40 amino acid-long Aβ (Aβ42 and Aβ40) in plasma to predict CNS amyloid status. Methodologies that quantitate Aβ42 and 40 peptides in blood via immunoassay or immunoprecipitation-mass spectrometry (IP-MS) were considered, and their ability to distinguish participants with amyloidosis compared to amyloid PET and CSF Aβ measures as reference standards was evaluated. Recent studies indicate that some IP-MS assays perform well in accurately and precisely measuring Aβ and detecting brain amyloid aggregates.
37.	Brounéus, Fredrik, et al. (författare) DN Debatt Repliker : ”Nej, vårt inlägg handlade inte om att ge upp kampen mot antibiotika” 2021 Ingår i: Dagens Nyheter. - Stockholm : AB Dagens nyheter. - 1101-2447. ; :2021-02-24 Tidskriftsartikel (populärvet., debatt m.m.)
38.	Brounéus, Fredrik, et al. (författare) DN Debatt Repliker. ”Nej, vårt inlägg handlade inte om att ge upp kampen mot antibiotika” : 10 forskare: Det handlar om hopp och en uppmaning till att vi ska bli fler som kämpar tillsammans. 2021 Ingår i: Dagens nyheter (DN debatt). - 1101-2447. Tidskriftsartikel (populärvet., debatt m.m.)
39.	Brounéus, Fredrik, et al. (författare) ”Vi måste förbereda oss för att antibiotika slutar fungera” 2021 Ingår i: Dagens nyheter (DN debatt). - 1101-2447. ; :2021-02-16 Tidskriftsartikel (populärvet., debatt m.m.)
40.	Brounéus, Fredrik, et al. (författare) ”Vi måste förbereda oss för att antibiotika slutar fungera” 2021 Ingår i: Dagens Nyheter. - Stockholm : AB Dagens nyheter. - 1101-2447. ; :2021-02-17 Tidskriftsartikel (populärvet., debatt m.m.)abstract 11 forskare: En framtid utan verksam antibiotika är inte nödvändigtvis ett undergångsscenario eller en nattsvart dystopi. Men samhällets alla sektorer måste förbereda sig i god tid. Då kan detta postantibiotiska samhälle mycket väl utgöra en levbar framtid.
41.	Brum, Wagner S., et al. (författare) Effect of Neprilysin Inhibition on Alzheimer Disease Plasma Biomarkers : A Secondary Analysis of a Randomized Clinical Trial 2024 Ingår i: JAMA Neurology. - 2168-6149. ; 81:2, s. 197-200 Tidskriftsartikel (refereegranskat)abstract Amyloid-β (Aβ) accumulation is critical in Alzheimer disease (AD), and neprilysin is involved in physiologically clearing Aβ. Concerns exist regarding long-term use of sacubitril/valsartan, a neprilysin inhibitor and angiotensin receptor blocker used for heart failure, and its potential to increase AD risk. We evaluated neprilysin inhibition’s effect on AD blood biomarkers in patients with coronary heart disease.
42.	Brönmark, Christer, et al. (författare) Ponds as experimental arenas for studying animal movement : current research and future prospects 2023 Ingår i: Movement Ecology. - 2051-3933. ; 11 Forskningsöversikt (refereegranskat)abstract Animal movement is a multifaceted process that occurs for multiple reasons with powerful consequences for food web and ecosystem dynamics. New paradigms and technical innovations have recently pervaded the field, providing increasingly powerful means to deliver fine-scale movement data, attracting renewed interest. Specifically in the aquatic environment, tracking with acoustic telemetry now provides integral spatiotemporal information to follow individual movements in the wild. Yet, this technology also holds great promise for experimental studies, enhancing our ability to truly establish cause-and-effect relationships. Here, we argue that ponds with well-defined borders (i.e. “islands in a sea of land”) are particularly well suited for this purpose. To support our argument, we also discuss recent experiences from studies conducted in an innovative experimental infrastructure, composed of replicated ponds equipped with modern aquatic telemetry systems that allow for unparalleled insights into the movement patterns of individual animals.
43.	Camporesi, Elena, et al. (författare) Neuroligin-1 in brain and CSF of neurodegenerative disorders: investigation for synaptic biomarkers 2021 Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Synaptic pathology is a central event in Alzheimer's disease (AD) and other neurodegenerative conditions, and investigation of synaptic proteins can provide valuable tools to follow synaptic dysfunction and loss in these diseases. Neuroligin-1 (Nlgn1) is a postsynaptic cell adhesion protein, important for synapse stabilization and formation. Nlgn1 has been connected to cognitive disorders, and specifically to AD, as target of the synaptotoxic effect of amyloid-beta (A beta) oligomers and A beta fibrils. To address changes in Nlgn1 expression in human brain, brain regions in different neurological disorders were examined by Western blot and mass spectrometry. Brain specimens from AD (n = 23), progressive supranuclear palsy (PSP, n = 11), corticobasal degeneration (CBD, n = 10), and Pick's disease (PiD, n = 9) were included. Additionally, cerebrospinal fluid (CSF) samples of AD patients (n = 43) and non-demented controls (n = 42) were analysed. We found decreased levels of Nlgn1 in temporal and parietal cortex (similar to 50-60% reductions) in AD brains compared with controls. In frontal grey matter the reduction was not seen for AD patients; however, in the same region, marked reduction was found for PiD (similar to 77%), CBD (similar to 66%) and to a lesser extent for PSP (similar to 43%), which could clearly separate these tauopathies from controls. The Nlgn1 level was reduced in CSF from AD patients compared to controls, but with considerable overlap. The dramatic reduction of Nlgn1 seen in the brain extracts of tauopathies warrants further investigation regarding the potential use of Nlgn1 as a biomarker for these neurodegenerative diseases.
44.	Castor, C, et al. (författare) Psychometric evaluation of the electronic faces thermometer scale for pain assessment in children 8–17years old: A study protocol 2023 Ingår i: Paediatric and Neonatal Pain. - : Wiley. - 2379-5824 .- 2637-3807. ; 5:4, s. 99-109 Tidskriftsartikel (refereegranskat)abstract It is often a challenge for a child to communicate their pain, and their possibilities to do so should be strengthened in healthcare settings. Digital self-assessment provides a potential solution for person-centered care in pain management and promotes child participation when a child is ill. A child's perception of pain assessment differs when it is assessed using digital or analog formats. As we move into the digital era, there is an urgent need to validate digital pain assessment tools, including the newly developed electronic Faces Thermometer Scale (eFTS). This study protocol describes three studies with the overall aim to evaluate psychometric properties of the eFTS for assessing pain in children 8–17years of age. A multi-site project design combining quantitative and qualitative methods will be used for three observational studies. Study 1: 100 Swedish-speaking children will report the level of anticipated pain from vignettes describing painful situations in four levels of pain and a think-aloud method will be used for data collection. Data will be analyzed with phenomenography as well as descriptive and comparative statistics. Study 2: 600 children aged 8–17years at pediatric and dental settings in Sweden, Denmark, Iceland, and USA will be included. Children will assess their pain intensity due to medical or dental procedures, surgery, or acute pain using three different pain Scales for each time point; the eFTS, the Faces Pain Scale Revised, and the Coloured Analogue Scale. Descriptive and comparative statistics will be used, with subanalysis taking cultural context into consideration. Study 3: A subgroup of 20 children out of these 600 children will be purposely included in an interview to describe experiences of grading their own pain using the eFTS. Qualitative data will be analyzed with content analysis. Our pilot studies showed high level of adherence to the study procedure and rendered only a small revision of background questionnaires. Preliminary analysis indicated that the instruments are adequate to be used by children and that the analysis plan is feasible. A digital pain assessment tool contributes to an increase in pain assessment in pediatric care. The Medical Research Council framework for complex interventions in healthcare supports a thorough development of a new scale. By evaluating psychometric properties in several settings by both qualitative and quantitative methods, the eFTS will become a well-validated tool to strengthen the child's voice within healthcare.
45.	Chetelat, G., et al. (författare) Amyloid-PET and 18-F-FDG-PET in the diagnostic investigation of Alzheimer's disease and other dementias 2020 Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 19:11, s. 951-962 Forskningsöversikt (refereegranskat)abstract Various biomarkers are available to support the diagnosis of neurodegenerative diseases in clinical and research settings. Among the molecular imaging biomarkers, amyloid-PET, which assesses brain amyloid deposition, and F-18-fluorodeoxyglucose (F-18-FDG) PET, which assesses glucose metabolism, provide valuable and complementary information. However, uncertainty remains regarding the optimal timepoint, combination, and an order in which these PET biomarkers should be used in diagnostic evaluations because conclusive evidence is missing. Following an expert panel discussion, we reached an agreement on the specific use of the individual biomarkers, based on available evidence and clinical expertise. We propose a diagnostic algorithm with optimal timepoints for these PET biomarkers, also taking into account evidence from other biomarkers, for early and differential diagnosis of neurodegenerative diseases that can lead to dementia. We propose three main diagnostic pathways with distinct biomarker sequences, in which amyloid-PET and F-18-FDG-PET are placed at different positions in the order of diagnostic evaluations, depending on clinical presentation. We hope that this algorithm can support diagnostic decision making in specialist clinical settings with access to these biomarkers and might stimulate further research towards optimal diagnostic strategies.
46.	Chinapah, Vinayagum, et al. (författare) COVID-19 Impacts on Education and the Need for Distance Education and Digital Solutions : An Ongoing Global Online survey 2021 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Our education community of learners, teachers, leaders, managers, providers, researchers, policymakers, together with the business community and other stakeholders, are all, and without any exception, here and elsewhere, in a dire learning-teaching, managing, and decision-making situation with the crisis from the COVID-19 pandemic. This abstract provides a brief from the Reaching Out ALL (ROA) initiative which maps the extent to which the needs and implications of Distance Education and Digital solutions may, with and without success, address COVID-19 impacts on education, locally, institutionally, nationally, and globally. COVID-19’s divide is of great concern for the successful and effective implementation of the Sustainable Development Goals (SDGs) and SDGs No.4, Quality Education, in particular. Educational actions reaching down the everyday learning-teaching contexts and conditions locally, nationally, and globally cannot be treated in the total absence and isolation of the direct voices and concerns, i.e., from those actual beneficiaries, partners, and targeted audience of our educational sector, from primary/basic up to the higher/university levels. This is the uniqueness of this present and ongoing global online survey. Its very purpose is in gathering the most updated and relevant empirical information and data on the impact of COVID-19 on education with a view to mapping the urgent and pressing needs for distance education and digital solutions. Can COVID-19 create new possibilities to mitigate the Divide in education, or does it just the contrary? Let us get from the direct voices. Mapping the improvements and/or shortcomings both prior to, and during COVID-19, on the access and quality of education offered, will assist the educational community in their choice of the most effective distance education and digital solutions The ROA initiative, which is introduced above, is based upon the collection, analysis and interpretation of data and information from an ongoing 3–5-minute Global Online Survey (GOS) on COVID-19 Impacts on Education. GOS was first launched in January 2021 worldwide, and will end by the end of April 2021 in several languages, namely English, Chinese, French, Spanish, Portuguese, Swedish, Arabic, Tigrinya, Bulgarian, and many other languages. The GOS survey is carried out by Stockholm University, Sweden, and its international partners. Distance education and digital solutions alone, can neither be of quality nor be effective, if the direct voices of the education community (learners, teachers, managers, researchers’ policymakers, providers, and parents, and so on) are neither heard and nor put into implementation. The COVID-19 Global Online Survey is an important, if not, a most vital initiative to reach this goal making education equally accessible, inclusive with quality, and sustainable through empirical evidence for relevant and appropriate informed decision-making and implementation.
47.	Cicognola, C., et al. (författare) Associations of CSF PDGFR & beta; With Aging, Blood-Brain Barrier Damage, Neuroinflammation, and Alzheimer Disease Pathologic Changes 2023 Ingår i: NEUROLOGY. - 0028-3878. ; 101:1 Tidskriftsartikel (refereegranskat)abstract Background and ObjectivesInjured pericytes in the neurovascular unit release platelet-derived growth factor & beta; (PDGFR & beta;) into the CSF. However, it is not clear how pericyte injury contributes to Alzheimer disease (AD)-related changes and blood-brain barrier (BBB) damage. We aimed to test whether CSF PDGFR & beta; was associated with different AD-associated and age-associated pathologic changes leading to dementia.MethodsPDGFR & beta; was measured in the CSF of 771 participants with cognitively unimpaired (CU, n = 408), mild cognitive impairment (MCI, n = 175), and dementia (n = 188) from the Swedish BioFINDER-2 cohort. We then checked association with & beta;-amyloid (A & beta;)-PET and tau-PET standardized uptake value ratio, APOE & epsilon;4 genotype and MRI measurements of cortical thickness, white matter lesions (WMLs), and cerebral blood flow. We also analyzed the role of CSF PDGFR & beta; in the relationship between aging, BBB dysfunction (measured by CSF/plasma albumin ratio, QAlb), and neuroinflammation (i.e., CSF levels of YKL-40 and glial fibrillary acidic protein [GFAP], preferentially expressed in reactive astrocytes).ResultsThe cohort had a mean age of 67 years (CU = 62.8, MCI = 69.9, dementia = 70.4), and 50.1% were male (CU = 46.6%, MCI = 53.7%, dementia = 54.3%). Higher CSF PDGFR & beta; concentrations were related to higher age (b = 19.1, & beta; = 0.5, 95% CI 16-22.2, p < 0.001), increased CSF neuroinflammatory markers of glial activation YKL-40 (b = 3.4, & beta; = 0.5, 95% CI 2.8-3.9, p < 0.001), GFAP (b = 27.4, & beta; = 0.4, 95% CI 20.9-33.9, p < 0.001), and worse BBB integrity measured by QAlb (b = 37.4, & beta; = 0.2, 95% CI 24.9-49.9, p < 0.001). Age was also associated with worse BBB integrity, and this was partly mediated by PDGFR & beta; and neuroinflammatory markers (16%-33% of total effect). However, PDGFR & beta; showed no associations with APOE & epsilon;4 genotype, PET imaging of A & beta; and tau pathology, or MRI measures of brain atrophy and WMLs (p > 0.05).DiscussionIn summary, pericyte damage, reflected by CSF PDGFR & beta;, may be involved in age-related BBB disruption together with neuroinflammation, but is not related to Alzheimer-related pathologic changes.
48.	Cicognola, Claudia, et al. (författare) Associations of CSF PDGFRβ With Aging, Blood-Brain Barrier Damage, Neuroinflammation, and Alzheimer Disease Pathologic Changes 2023 Ingår i: Neurology. - 1526-632X. ; 101:1, s. 30-39 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND OBJECTIVES: Injured pericytes in the neurovascular unit release platelet-derived growth factor β (PDGFRβ) into the cerebrospinal fluid (CSF). However, it is not clear how pericyte injury contributes to Alzheimer's disease (AD)-related changes and blood brain barrier (BBB) damage. We aimed to test if CSF PDGFRβ was associated with different AD- and age-associated pathological changes leading to dementia.METHODS: PDGFRβ was measured in the CSF of 771 cognitively unimpaired (CU, n=408), mild cognitive impairment (MCI, n=175) and dementia subjects (n=188) from the Swedish BioFINDER-2 cohort. We then checked association Aβ-PET and tau-PET SUVR, APOE ε4 genotype and MRI measurements of cortical thickness, white matter lesions (WML) and cerebral blood flow (CBF). We also analysed the role of CSF PDGFRβ in the relationship between aging, BBB dysfunction (measured by CSF/plasma albumin ratio, QAlb) and neuroinflammation (i.e., CSF levels of YKL-40 and glial fibrillary acidic protein [GFAP], preferentially expressed in reactive astrocytes). RESULTS: The cohort had a mean age of 67 years (CU=62.8, MCI=69.9, dementia=70.4) and 50.1% were male (CU=46.6%, MCI=53.7%, dementia=54.3%). Higher CSF PDGFRβ concentrations were related to higher age (b=19.1, β=0.5, 95% CI=16-22.2, p<0.001), increased CSF neuroinflammatory markers of glial activation YKL-40 (b=3.4, β=0.5, 95% CI=2.8-3.9, p<0.001) and GFAP (b=27.4, β=0.4, 95% CI=20.9-33.9, p<0.001), and worse BBB integrity measured by QAlb (b=37.4, β=0.2, 95% CI=24.9-49.9, p<0.001). Age was also associated with worse BBB integrity, and this was partly mediated by PDGFRβ and neuroinflammatory markers (16-33% of total effect). However, PDGFRβ showed no associations with APOE ε4 genotype, PET imaging of Aβ and tau pathology or MRI measures of brain atrophy and white matter lesions (p>0.05).DISCUSSION: In summary, pericyte damage, reflected by CSF PDGFRβ, may be involved in age-related BBB disruption together with neuroinflammation, but is not related to Alzheimer-related pathological changes.
49.	Cicognola, Claudia, et al. (författare) Cerebrospinal fluid N-224 tau helps discriminate Alzheimer's disease from subjective cognitive decline and other dementias 2021 Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1 Tidskriftsartikel (refereegranskat)abstract Background Elevated cerebrospinal fluid (CSF) concentrations of total tau (T-tau) and phosphorylated tau at Thr181 (P-tau181) protein are typical of Alzheimer's disease (AD). However, the T-tau assay measures only the mid-region of the protein, while tau in CSF is instead composed of a series of fragments. One fragment species in particular, N-224, shows increased levels in AD compared to controls. In this multicentre study, we performed a clinical validation of the N-224 assay in cohorts including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, non-AD dementias and controls. Methods Cohorts consisted of 30 SCD and 30 probable AD from the Amsterdam Dementia Cohort (cohort 1) and 539 controls, 195 SCD, 232 MCI, 137 AD and 253 non-AD from the Swedish BioFINDER study (cohort 2). All samples had AD core biomarkers (A beta 42, T-tau, P-tau181) measurements. N-224 was measured with an in-house ultrasensitive Simoa assay. Results N-224 levels were significantly higher in AD compared to SCD (cohort 1: p = 0.003) and in AD compared to all other diagnostic groups in cohort 2 (control, SCD, MCI and non-AD, p < 0.0001). Within the non-AD group, N-224 showed significantly lower concentrations compared to AD in Parkinson's disease (PD, p < 0.0001), Parkinson's disease dementia (PDD, p = 0.004), progressive supranuclear palsy (PSP, < 0.0001), multiple system atrophy (MSA, p = 0.002) and parkinsonisms not otherwise specified (NOS, p = 0.007). In cohort 1, higher concentrations of N-224 were associated to lower Mini-Mental State Examination (MMSE) scores (R-2 = 0.318, beta = 0.564, p <= 0.0001) and could accurately identify a pathological (< 24) MMSE score (p < 0.0001, AUC = 0.824). Conclusions N-224 tau can distinguish AD subjects from SCD and can discriminate subgroups of non-AD dementias from AD. Therefore, N-224 may be a useful addition to the tau biomarker toolbox for the study of tau species in CSF and for better understanding disease pathogenesis.
50.	Cicognola, Claudia, et al. (författare) Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment 2021 Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1 Tidskriftsartikel (refereegranskat)abstract Introduction: Plasma glial fibrillary acidic protein (GFAP) is a marker of astroglial activation and astrocytosis. We assessed the ability of plasma GFAP to detect Alzheimer’s disease (AD) pathology in the form of AD-related amyloid-β (Aβ) pathology and conversion to AD dementia in a mild cognitive impairment (MCI) cohort. Method: One hundred sixty MCI patients were followed for 4.7 years (average). AD pathology was defined using cerebrospinal fluid (CSF) Aβ42/40 and Aβ42/total tau (T-tau). Plasma GFAP was measured at baseline and follow-up using Simoa technology. Results: Baseline plasma GFAP could detect abnormal CSF Aβ42/40 and CSF Aβ42/T-tau with an AUC of 0.79 (95% CI 0.72–0.86) and 0.80 (95% CI 0.72–0.86), respectively. When also including APOE ε4 status as a predictor, the accuracy of the model to detect abnormal CSF Aβ42/40 status improved (AUC = 0.86, p = 0.02). Plasma GFAP predicted subsequent conversion to AD dementia with an AUC of 0.84 (95% CI 0.77–0.91), which was not significantly improved when adding APOE ε4 or age as predictors to the model. Longitudinal GFAP slopes for Aβ-positive and MCI who progressed to dementia (AD or other) were significantly steeper than those for Aβ-negative (p = 0.007) and stable MCI (p < 0.0001), respectively. Conclusion: Plasma GFAP can detect AD pathology in patients with MCI and predict conversion to AD dementia.

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