| 1. |
- Allard, Christina, et al.
(författare)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
- 2015
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Annan publikation (populärvet., debatt m.m.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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| 2. |
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| 3. |
- Chavez, Zuhara, et al.
(författare)
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Digital Tools and Information Needs Assessment for Efficient Deviation Handling in SMEs
- 2020
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Ingår i: Advances in Transdisciplinary Engineering at SPS2020. - : IOS Press BV. - 9781614994398 ; , s. 24-35
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Konferensbidrag (refereegranskat)abstract
- In a time of change focusing on the application of technology, there is a high risk of underestimating the compliance of internal needs and adaption to context. The research study employs a qualitative approach using the case study methodology. The source of data comes from five different manufacturing companies categorized as Small to Medium Size Enterprises (SMEs). A multidisciplinary team performed semi-structured interviews and fieldwork at each site, along with regular online meetings with the partners. The study employs five dimensions of the information quality perspective to assess information utilized to support deviation handling and connects the information quality deficiencies to the digital tools' impact. The empirical findings indicate the need for the companies to perform a requirement analysis of information needs before the adoption of digital systems or digital tools, to assess their current state in terms of data and information. The paper discusses the impact digital tools may have on deviation management in SMEs and under which circumstances digital tools could improve deviation management. Lastly, this paper intends to shed light on the utilization of digital technologies for disturbance handling on the production shop floor. © 2020 The authors
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| 4. |
- Furukawa, Toshi A., et al.
(författare)
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Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression : a systematic review and component network meta-analysis using individual data
- 2021
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Ingår i: Lancet psychiatry. - London, United Kingdom : Elsevier. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511
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Forskningsöversikt (refereegranskat)abstract
- Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511
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| 5. |
- Hermansson, Michael, 1966, et al.
(författare)
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Esophageal perforation in South of Sweden: results of surgical treatment in 125 consecutive patients.
- 2010
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Ingår i: BMC surgery. - : Springer Science and Business Media LLC. - 1471-2482. ; 10
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- For many years there has been a debate as to which is the method of choice in treating patients with esophageal perforation. The literature consists mainly of small case series. Strategies for aiding patients struck with this disease is changing as new and less traumatic treatment options are developing. We studied a relatively large consecutive material of esophageal perforations in an effort to evaluate prognostic factors, diagnostic efforts and treatment strategy in these patients.
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| 6. |
- Johansson, Maurits, et al.
(författare)
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Apathy and anxiety are early markers of Alzheimer's disease
- 2020
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 85, s. 74-82
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we investigated associations between neuropsychiatric symptoms (i.e., apathy, anxiety, and depression) and cerebral atrophy, white matter lesions (WML), beta-amyloid (A beta) deposition, and cognitive decline in a nondemented sample. 104 cognitively unimpaired and 53 subjects with mild cognitive impairment were followed for up to 4 years within the Swedish BioFINDER study. Neuropsychiatric assessments included the Hospital Anxiety and Depression Scale and the Apathy Evaluation Scale. Magnetic resonance imaging and F-18-flutemetamol-positron emission tomography quantified brain atrophy, WML, and A beta deposition. Mini-Mental State Examination assessed longitudinal global cognition. Regression analyses were used to test for associations. Apathy and anxiety were shown related to A beta deposition and predicted cognitive decline. Anxiety also interacted with amyloid status to predict faster cognitive deterioration. Apathy was further related to frontotemporal and subcortical atrophy, as well as WML. To conclude, the associations between apathy and anxiety with A beta deposition and cognitive decline point to these symptoms as early clinical manifestations of Alzheimer's disease. (C) 2019 Elsevier Inc. All rights reserved.
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| 7. |
- Johansson, Maurits, et al.
(författare)
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Mild behavioral impairment and its relation to tau pathology in preclinical Alzheimer's disease
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Mild behavioral impairment (MBI) is suggested as risk marker for neurodegenerative diseases, such as Alzheimer's disease (AD). Recently, pathologic tau deposition in the brain has been shown closely related to clinical manifestations, such as cognitive deficits. Yet, associations between tau pathology and MBI have rarely been investigated. It is further debated if MBI precedes cognitive deficits in AD. Here, we explored potential mechanisms by which MBI is related to AD, this by studying associations between MBI and tau in preclinical AD. In all, 50 amyloid-beta -positive cognitively unimpaired subjects (part of the BioFINDER-2 study) underwent MBI-checklist (MBI-C) to assess MBI, and the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) delayed word recall (ADAS-DR) to assess episodic memory. Early tau pathology was determined using tau-PET ([F-18]RO948 retention in entorhinal cortex/hippocampus) and cerebrospinal fluid (CSF) P-tau(181). Regression models were used to test for associations. We found that higher tau-PET signal in the entorhinal cortex/hippocampus and CSF P-tau(181) levels were associated with higher MBI-C scores (beta =0.010, SE=0.003, p=0.003 and beta =1.263, SE=0.446, p=0.007, respectively). When MBI-C and ADAS-DR were entered together in the regression models, tau-PET (beta =0.009, p=0.009) and CSF P-tau(181) (beta =0.408, p=0.006) were predicted by MBI-C, but not ADAS-DR. We conclude that in preclinical AD, MBI is associated with tau independently from memory deficits. This denotes MBI as an important early clinical manifestation related to tau pathology in AD.
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| 8. |
- Johansson, Maurits, et al.
(författare)
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Psychometric testing of a Swedish version of the Apathy Evaluation Scale
- 2017
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 71:6, s. 477-484
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Tidskriftsartikel (refereegranskat)abstract
- Background: Apathy, a prevalent and clinically relevant symptom in neurodegenerative disease, is often evaluated by the instrument Apathy Evaluation Scale (AES). However, this instrument has not been translated into Swedish, halting clinical and research efforts. Furthermore, previous studies lack analyses of some basic properties, such as the legitimacy of a total score, or have analysed dimensionality by questionable methods.Aim: To translate and psychometrically evaluate a Swedish version of the AES.Method: The AES was translated, and its psychometric properties were tested in the Swedish BioFINDER study, including cognitively well elderly, and subjects with mild cognitive or parkinsonian symptoms. Psychometric analyses were conducted according to classical test theory (CTT) and aimed to resemble those performed in the English original study by Marin etal. in 1991. Dimensionality was additionally analysed on a matrix of polychoric correlations and parallel analyses.Results: Data indicate that the Swedish AES performs satisfactorily regarding data completeness, scaling assumptions, targeting, and reliability. Principal component analyses (with parallel analysis) of polychoric correlation matrices identified a single component. Convergent and discriminative validity correlations accorded with a priori expectations.Conclusions: The study provides initial support that this Swedish AES performs similarly to the English original, and exhibits acceptable psychometric properties according to CTT, including supported unidimensionality, and may be adopted for use in clinical and research settings.
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| 9. |
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| 10. |
- Johansson, Per, 1966, et al.
(författare)
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Cerebrospinal fluid substance P concentrations are elevated in patients with Alzheimer's disease.
- 2015
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Ingår i: Neuroscience letters. - : Elsevier BV. - 1872-7972 .- 0304-3940. ; 609, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptides substance P, orexin A (hypocretin-1) and neurotensin are signaling molecules that influence brain activity. We examined their cerebrospinal fluid (CSF) levels in a study population consisting of Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n=32), stable MCI (SMCI, n=13), other dementias (n=15), and healthy controls (n=20). CSF substance P level was increased in AD patients compared to patients with other dementias and healthy controls (P<0.05 and P<0.01, respectively). Patients with other dementia or SMCI had lower CSF orexin A level than AD patients (both P<0.05) and marginally lower level than healthy controls (both P=0.05). CSF neurotensin level was similar in all groups. In the total study population (n=80), CSF substance P level correlated positively with CSF levels of T-tau and P-tau, and in AD patients (n=32), CSF substance P level correlated positively with CSF Aβ1-42 level. In conclusion, CSF substance P level was elevated in AD patients and correlated with CSF Aβ1-42 level, a well established marker of senile plaque pathology. The role of low CSF orexin A level in other dementias or SMCI needs to be explored in further studies.
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| 11. |
- Johansson, Per, 1966, et al.
(författare)
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Mild dementia is associated with increased adrenal secretion of cortisol and precursor sex steroids in women.
- 2011
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Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 75:3, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- Context Sex steroid levels decrease with increasing age, but little is known whether this is of importance for the age-related decline in cognitive function. Design and patients A cross-sectional study of 50 (26 men) consecutive patients under primary evaluation of cognitive impairment (D group) and 18 (9 men) matched healthy controls (C group). Measurements Sex steroid and precursor levels were determined in serum and, when measurable, in cerebrospinal fluid (CSF) using gas chromatography/mass spectroscopy (GC-MS) or liquid chromatography/mass spectroscopy (LC-MS). Sex hormone binding globulin (SHBG) and cortisol concentrations were measured using conventional assays. Results Patients in the D group had higher 24-h urine cortisol levels and increased serum levels of dehydroepiandrosterone (DHEA) and its sulphate ester dihydroepiandrosterone sulphate (DHEAS), androsterone (ADT), and oestrone (E1) and its sulphate ester E1S, compared with the controls. When men and women were analysed separately, increased serum concentrations of E1 and E1S were observed in both D men and D women, whereas increased levels of other sex steroids and cortisol were seen only in D women. Conclusions In both D men and women, serum E1 and E1S levels were increased, whereas other changes were gender specific and only seen in D women. Further studies are needed to determine whether these changes are a cause of, or merely a consequence of, cognitive impairment in elderly subjects.
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| 12. |
- Johansson, Per, 1966, et al.
(författare)
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Reduced Cerebrospinal Fluid Concentration of Apolipoprotein A-I in Patients with Alzheimer's Disease.
- 2017
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908 .- 1387-2877. ; 59:3, s. 1017-1026
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E (ApoE) has been extensively studied in Alzheimer's disease (AD), but little is known of apolipoprotein A-I (ApoA-I) in cerebrospinal fluid (CSF).Plasma lipids as well as ApoA-I and ApoE in plasma and CSF were determined and related to Mini-Mental State Examination (MMSE) score, APOE genotype, and CSF AD biomarkers.Consecutive patients with AD (n=29), stable mild cognitive impairment (n=13), other dementias (n=14), and healthy controls (n=18) were included at a single center.AD patients had higher plasma triglycerides and lower CSF ApoA-I concentration than controls (both p<0.05). CSF ApoE concentration was reduced in other dementias (p<0.01). In AD as well as other dementias, the ratios between CSF and plasma concentrations of both ApoA-I and ApoE were lower than those in the controls. ApoA-I and ApoE in plasma and CSF were not influenced by APOEɛ4 allele distribution. In the total study population (n=74), CSF ApoA-I correlated positively with MMSE score (r=0.26, p<0.05) and negatively with CSF P-tau (r=-0.25, p<0.05). CSF ApoE correlated positively with CSF concentrations of T-tau and P-tau in the total study population and in AD patients.CSF ApoA-I was reduced in AD patients and associated with measures of cognitive function and AD disease status. The mechanisms underlying the decreased CSF:plasma ratios of ApoA-I and ApoE in AD and other dementias need to be explored in further studies.
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| 13. |
- Johansson, Per, 1966, et al.
(författare)
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Reduced cerebrospinal fluid concentration of interleukin-12/23 subunit p40 in patients with cognitive impairment.
- 2017
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- The role of inflammation in Alzheimer's disease (AD) and other cognitive disorders is unclear. In a well-defined mono-center population, we measured cytokines and chemokines in paired serum and cerebrospinal fluid (CSF) samples.Consecutive patients with AD (n = 30), stable mild cognitive impairment (SMCI, n = 11), other dementias (n = 11), and healthy controls (n = 18) were included. None of the subjects was treated with glucocorticoids, cholinesterase inhibitors, or non-steroidal anti-inflammatory drugs. Serum and CSF concentrations of interleukin-6 (IL-6), IL-8, IL-12/23 p40, IL-15, IL-16, vascular endothelial growth factor-A (VEGF-A), and three chemokines were measured using a multiplex panel.After correction for multiple comparisons, only CSF IL-12/23 p40 concentration differed significantly between the total patient group (n = 52) and controls (n = 18; p = 0.002). Further analyses showed that CSF IL-12/23 p40 concentration was decreased in all patient subgroups (AD, other dementias, and SMCI) compared to healthy controls (p < 0.01, p < 0.05, and p < 0.05, respectively). In the total study population (n = 70), CSF IL-12/23 p40 concentrations correlated positively with CSF concentrations of β-amyloid1-42 (Aβ1-42) and phosphorylated tau protein (P-tau) whereas in AD patients (n = 30), CSF IL-12/23 p40 only correlated positively with CSF P-Tau (r = 0.46, p = 0.01).Most cytokines and chemokines were similar in patients and controls, but CSF IL-12/23 subunit p40 concentration was decreased in patients with cognitive impairment, and correlated with markers of AD disease status. Further studies are needed to evaluate the role of CSF IL-12/23 p40 in other dementias and SMCI.
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| 14. |
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| 15. |
- Pesonen, Ida, et al.
(författare)
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High prevalence of interstitial lung abnormalities in middle-aged never-smokers
- 2023
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms.METHODS: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing.FINDINGS: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA.INTERPRETATION: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.
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| 16. |
- Wagner, J., et al.
(författare)
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First 230? : GHz VLBI fringes on 3C 279 using the APEX Telescope (Research Note)
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 581
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We report about a 230? GHz very long baseline interferometry (VLBI) fringe finder observation of blazar 3C 279 with the APEX telescope in Chile, the phased submillimeter array (SMA), and the SMT of the Arizona Radio Observatory (ARO). Methods. We installed VLBI equipment and measured the APEX station position to 1? cm accuracy (1σ). We then observed 3C 279 on 2012 May 7 in a 5? h 230? GHz VLBI track with baseline lengths of 2800? Mλ to 7200? Mλ and a finest fringe spacing of 28.6? μas. Results. Fringes were detected on all baselines with signal-to-noise ratios of 12 to 55 in 420? s. The correlated flux density on the longest baseline was ∼0.3? Jy beam-1, out of a total flux density of 19.8? Jy. Visibility data suggest an emission region ≤ 38? μas in size, and at least two components, possibly polarized. We find a lower limit of the brightness temperature of the inner jet region of about 1010? K. Lastly, we find an upper limit of 20% on the linear polarization fraction at a fringe spacing of ∼ 38? μas. Conclusions. With APEX the angular resolution of 230? GHz VLBI improves to 28.6? μas. This allows one to resolve the last-photon ring around the Galactic Center black hole event horizon, expected to be 40? μas in diameter, and probe radio jet launching at unprecedented resolution, down to a few gravitational radii in galaxies like M 87. To probe the structure in the inner parsecs of 3C 279 in detail, follow-up observations with APEX and five other mm-VLBI stations have been conducted (March 2013) and are being analyzed.
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| 17. |
- Wallin, Anders, 1950, et al.
(författare)
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Cognitive medicine - a new approach in health care science.
- 2018
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Ingår i: BMC psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- The challenges of today's society call for more knowledge about how to maintain all aspects of cognitive health, such as speed/attention, memory/learning, visuospatial ability, language, executive capacity and social cognition during the life course.Medical advances have improved treatments of numerous diseases, but the cognitive implications have not been sufficiently addressed. Disability induced by cognitive dysfunction is also a major issue in groups of patients not suffering from Alzheimer's disease or related disorders. Recent studies indicate that several negative lifestyle factors can contribute to the development of cognitive impairment, but intervention and prevention strategies have not been implemented. Disability due to cognitive failure among the workforce has become a major challenge. Globally, the changing aging pyramid results in increased prevalence of cognitive disorders, and the diversity of cultures influences the expression, manifestation and consequences of cognitive dysfunction.Major tasks in the field of cognitive medicine are basic neuroscience research to uncover diverse disease mechanisms, determinations of the prevalence of cognitive dysfunction, health-economical evaluations, and intervention studies. Raising awareness for cognitive medicine as a clinical topic would also highlight the importance of specialized health care units for an integrative approach to the treatment of cognitive dysfunctions.
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| 18. |
- Wasteson, Per, 1974, et al.
(författare)
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Developmental origin of smooth muscle cells in the descending aorta in mice.
- 2008
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 135:10, s. 1823-32
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Tidskriftsartikel (refereegranskat)abstract
- Aortic smooth muscle cells (SMCs) have been proposed to derive from lateral plate mesoderm. It has further been suggested that induction of SMC differentiation is confined to the ventral side of the aorta, and that SMCs later migrate to the dorsal side. In this study, we investigate the origin of SMCs in the descending aorta using recombination-based lineage tracing in mice. Hoxb6-cre transgenic mice were crossed with Rosa 26 reporter mice to track cells of lateral plate mesoderm origin. The contribution of lateral plate mesoderm to SMCs in the descending aorta was determined at different stages of development. SMC differentiation was induced in lateral plate mesoderm-derived cells on the ventral side of the aorta at embryonic day (E) 9.0-9.5, as indicated by expression of the SMC-specific reporter gene SM22alpha-lacZ. There was, however, no migration of SMCs from the ventral to the dorsal side of the vessel. Moreover, the lateral plate mesoderm-derived cells in the ventral wall of the aorta were replaced by somite-derived cells at E10.5, as indicated by reporter gene expression in Meox1-cre/Rosa 26 double transgenic mice. Examination of reporter gene expression in adult aortas from Hoxb6-cre/Rosa 26 and Meox1-cre/Rosa 26 double transgenic mice suggested that all SMCs in the adult descending aorta derive from the somites, whereas no contribution was recorded from lateral plate mesoderm.
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| 19. |
- Åberg, Daniel, 1973, et al.
(författare)
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Increased Cerebrospinal Fluid Level of Insulin-like Growth Factor-II in Male Patients with Alzheimer's Disease
- 2015
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 48:3, s. 637-646
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insulin-like growth factor-II (IGF-II) is important for brain development. Although IGF-II is abundant also in adult life, little is known of the role of IGF-II in Alzheimer's disease (AD). Objective and methods: This was a cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n = 32), stable MCI (SMCI, n = 13), or other dementias (n = 15). IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 were analyzed in serum and cerebrospinal fluid (CSF). Results: Levels of IGF-II, IGFBP-1, and IGFBP-2 were similar in all groups in the total study population. Gender-specific analyses showed that in men (n = 40), CSF IGF-II level was higher in AD compared to SMCI and controls (p < 0.01 and p < 0.05, respectively). Furthermore, CSF IGFBP-2 levelwas increased inADmen versus SMCI men (p < 0.01) and tended to be increased versus control men (p = 0.09). There were no between-group differences in women (n = 40). In the total study population (n = 80) as well as in men (n = 40), CSF levels of IGF-II and IGFBP-2 correlated positively with CSF levels of the AD biomarkers total-tau and phosphorylated tau protein. Conclusion: In men, but not women, in the early stages of AD, CSF IGF-II level was elevated, and CSF IGFBP-2 level tended to be increased, compared to healthy controls.
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| 20. |
- Ahlström, Katarina, 1966, et al.
(författare)
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Metabolic responses in ischemic myocardium after inhalation of carbon monoxide.
- 2009
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Ingår i: Acta Anaesthesiol Scand. - : Wiley. - 1399-6576 .- 0001-5172. ; 53:8, s. 1036-42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To clarify the mechanisms of carbon monoxide (CO) tissue-protective effects, we studied energy metabolism in an animal model of acute coronary occlusion and pre-treatment with CO. METHODS: In anesthetized pigs, a coronary snare and microdialysis probes were placed. CO (carboxyhemoglobin 5%) was inhaled for 200 min in test animals, followed by 40 min of coronary occlusion. Microdialysate was analyzed for lactate and glucose, and myocardial tissue samples were analyzed for adenosine tri-phosphate, adenosine di-phosphate, and adenosine mono-phosphate. RESULTS: Lactate during coronary occlusion was approximately half as high in CO pre-treated animals and glucose levels decreased to a much lesser degree during ischemia. Energy charge was no different between groups. CONCLUSIONS: CO in the low-doses tested in this model results in a more favorable energy metabolic condition in that glycolysis is decreased in spite of maintained energy charge. Further work is warranted to clarify the possible mechanistic role of energy metabolism for CO protection.
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| 21. |
- Al-Amin, Rasel A., 1983-, et al.
(författare)
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Target Engagement-Mediated Amplification for Monitoring Drug-Target Interactions in Situ
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- It is important to determine the localization of drugs or drug candidates at cellular and subcellular resolution in relevant clinical specimens. This is necessary to evaluate drug candidates from early stages of drug development to clinical evaluation of mutations potentially causing resistance to targeted therapy. We describe a technology where oligonucleotide-conjugated drug molecules are used to visualize and measure target engagement in situ via rolling-circle amplification (RCA) of circularized oligonucleotide probes (padlock probes). We established this target engagement-mediated amplification (TEMA) technique using kinase inhibitor precursor compounds, and we applied the assay to investigate target interactions by microscopy in pathology tissue sections and using flow cytometry for blood samples from patients, as well as in commercial arrays including almost half of all human proteins. In the variant proxTEMAtechnique, in situ proximity ligation assays were performed by combining drug-DNA conjugates with antibody-DNA conjugates to specifically reveal drug binding to particular on- or off-targets in pathological tissues sections. In conclusion, the TEMA methods successfully visualize drug-target interaction by experimental and clinically approved kinase inhibitors in situ and with kinases among a large collection of arrayed proteins.
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| 22. |
- Ali, Muhammad, et al.
(författare)
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Leveraging large multi-center cohorts of Alzheimer disease endophenotypes to understand the role of Klotho heterozygosity on disease risk.
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:5
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Tidskriftsartikel (refereegranskat)abstract
- Two genetic variants in strong linkage disequilibrium (rs9536314 and rs9527025) in the Klotho (KL) gene, encoding a transmembrane protein, implicated in longevity and associated with brain resilience during normal aging, were recently shown to be associated with Alzheimer disease (AD) risk in cognitively normal participants who are APOE ε4 carriers. Specifically, the participants heterozygous for this variant (KL-SVHET+) showed lower risk of developing AD. Furthermore, a neuroprotective effect of KL-VSHET+ has been suggested against amyloid burden for cognitively normal participants, potentially mediated via the regulation of redox pathways. However, inconsistent associations and a smaller sample size of existing studies pose significant hurdles in drawing definitive conclusions. Here, we performed a well-powered association analysis between KL-VSHET+ and five different AD endophenotypes; brain amyloidosis measured by positron emission tomography (PET) scans (n = 5,541) or cerebrospinal fluid Aβ42 levels (CSF; n = 5,093), as well as biomarkers associated with tau pathology: the CSF Tau (n = 5,127), phosphorylated Tau (pTau181; n = 4,778) and inflammation: CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2; n = 2,123) levels. Our results found nominally significant associations of KL-VSHET+ status with biomarkers for brain amyloidosis (e.g., CSF Aβ positivity; odds ratio [OR] = 0.67 [95% CI, 0.55-0.78], β = 0.72, p = 0.007) and tau pathology (e.g., biomarker positivity for CSF Tau; OR = 0.39 [95% CI, 0.19-0.77], β = -0.94, p = 0.007, and pTau; OR = 0.50 [95% CI, 0.27-0.96], β = -0.68, p = 0.04) in cognitively normal participants, 60-80 years old, who are APOE e4-carriers. Our work supports previous findings, suggesting that the KL-VSHET+ on an APOE ε4 genotype background may modulate Aβ and tau pathology, thereby lowering the intensity of neurodegeneration and incidence of cognitive decline in older controls susceptible to AD.
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| 23. |
- Andersson, Gerhard, 1966-, et al.
(författare)
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Cognitive bias via the Internet : A comparison of web-based and standard emotional Stroop tasks in social phobia
- 2006
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Ingår i: Cognitive Behaviour Therapy. - : Informa UK Limited. - 1650-6073 .- 1651-2316. ; 35:1, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- There is accumulating evidence to suggest that social phobia is associated with attentional bias for words related to social threat. Information processing in individuals with social phobia (n = 87) was investigated in the present study using 2 versions of the emotional Stroop task. Results from a standard emotional Stroop task indicated delayed colour naming of socially threatening words relative to neutral words, in line with previous research, whereas results from a Web-based emotional Stroop task indicated a facilitation effect, with faster manual indication of colour choice for socially threatening words than for neutral words. Possible explanations for these contrasting findings and issues for further research are discussed. © 2006 Taylor & Francis.
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| 24. |
- Andersson, Gerhard, 1966-, et al.
(författare)
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Stroop facilitation in tinnitus patients : An experiment conducted via the World Wide Web
- 2005
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Ingår i: Cyberpsychology & Behavior. - : Mary Ann Liebert Inc. - 1094-9313 .- 1557-8364. ; 8:1, s. 32-38
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive mechanisms have been proposed to play an important role in tinnitus. In the present study, tinnitus participants were administered an emotional Stroop test via the Internet, incorporating words related to tinnitus concerns. In line with previous research using this Web-based version of the emotional Stroop test, faster color naming was demonstrated for concern-relevant words relative to neutral words. The present results thus provided support for a role for cognitive factors that are important for the understanding of tinnitus. However, future research is warranted in order to clarify the precise mechanisms involved in tinnitus-related Stroop effects. 1© Mary Ann Liebert, Inc.
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| 25. |
- Angelov, Angel G., 1983-
(författare)
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Methods for interval-censored data and testing for stochastic dominance
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis includes four papers: the first three of them are concerned with methods for interval-censored data, while the forth paper is devoted to testing for stochastic dominance.In many studies, the variable of interest is observed to lie within an interval instead of being observed exactly, i.e., each observation is an interval and not a single value. This type of data is known as interval-censored. It may arise in questionnaire-based studies when the respondent gives an answer in the form of an interval without having pre-specified ranges. Such data are called self-selected interval data. In this context, the assumption of noninformative censoring is not fulfilled, and therefore the existing methods for interval-censored data are not necessarily applicable.A problem of interest is to estimate the underlying distribution function. There are two main approaches to this problem: (i) parametric estimation, which assumes a particular functional form of the distribution, and (ii) nonparametric estimation, which does not rely on any distributional assumptions. In Paper A, a nonparametric maximum likelihood estimator for self-selected interval data is proposed and its consistency is shown. Paper B suggests a parametric maximum likelihood estimator. The consistency and asymptotic normality of the estimator are proven.Another interesting problem is to infer whether two samples arise from identical distributions. In Paper C, nonparametric two-sample tests suitable for self-selected interval data are suggested and their properties are investigated through simulations.Paper D concerns testing for stochastic dominance with uncensored data. The paper explores a testing problem which involves four hypotheses, that is, based on observations of two random variables X and Y, one wants to discriminate between four possibilities: identical survival functions, stochastic dominance of X over Y, stochastic dominance of Y over X, or crossing survival functions. Permutation-based tests suitable for two independent samples and for paired samples are proposed. The tests are applied to data from an experiment concerning the individual's willingness to pay for a given environmental improvement.
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| 26. |
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| 27. |
- Bäckström, Torbjörn, et al.
(författare)
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Isoallopregnanolone inhibits estrus cycle-dependent aggressive behavior
- 2023
-
Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 13:6
-
Tidskriftsartikel (refereegranskat)abstract
- Among female rats, some individuals show estrus cycle-dependent irritability/aggressive behaviors, and these individual rats may be used as a model for premenstrual dysphoric disorder (PMDD). We wanted to investigate if these behaviors are related to the estrus cycle phase containing moderately increased levels of positive GABA-A receptor-modulating steroids (steroid-PAM), especially allopregnanolone (ALLO), and if the adverse behavior can be antagonized. The electrophysiology studies in this paper show that isoallopregnanolone (ISO) is a GABA-A-modulating steroid antagonist (GAMSA), meaning that ISO can antagonize the agonistic effects of positive GABA-A receptor-modulating steroids in both α1β2γ2L and α4β3δ GABA-A receptor subtypes. In this study, we also investigated whether ISO could antagonize the estrus cycle-dependent aggressive behaviors in female Wistar rats using a resident–intruder test. Our results confirmed previous reports of estrus cycle-dependent behaviors in that 42% of the tested rats showed higher levels of irritability/aggression at diestrus compared to those at estrus. Furthermore, we found that, during the treatment with ISO, the aggressive behavior at diestrus was alleviated to a level comparable to that of estrus. We noticed an 89% reduction in the increase in aggressive behavior at diestrus compared to that at estrus. Vehicle treatment in the same animals showed a minimal effect on the diestrus-related aggressive behavior. In conclusion, we showed that ISO can antagonize Steroid-PAM both in α1β2γ2L and α4β3δ GABA-A receptor subtypes and inhibit estrus cycle-dependent aggressive behavior.
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| 28. |
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| 29. |
- Deming, Y., et al.
(författare)
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The MS4A gene cluster is a key modulator of soluble TREM2 and Alzheimer's disease risk
- 2019
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 11:505
-
Tidskriftsartikel (refereegranskat)abstract
- Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) has been associated with Alzheimer's disease (AD). TREM2 plays a critical role in microglial activation, survival, and phagocytosis; however, the pathophysiological role of sTREM2 in AD is not well understood. Understanding the role of sTREM2 in AD may reveal new pathological mechanisms and lead to the identification of therapeutic targets. We performed a genome-wide association study (GWAS) to identify genetic modifiers of CSF sTREM2 obtained from the Alzheimer's Disease Neuroimaging Initiative. Common variants in the membrane-spanning 4-domains subfamily A (MS4A) gene region were associated with CSF sTREM2 concentrations (rs1582763; P = 1.15 x 10(-15)); this was replicated in independent datasets. The variants associated with increased CSF sTREM2 concentrations were associated with reduced AD risk and delayed age at onset of disease. The single-nucleotide polymorphism rs1582763 modified expression of the MS4A4A and MS4A6A genes in multiple tissues, suggesting that one or both of these genes are important for modulating sTREM2 production. Using human macrophages as a proxy for microglia, we found that MS4A4A and TREM2 colocalized on lipid rafts at the plasma membrane, that sTREM2 increased with MS4A4A overexpression, and that silencing of MS4A4A reduced sTREM2 production. These genetic, molecular, and cellular findings suggest that MS4A4A modulates sTREM2. These findings also provide a mechanistic explanation for the original GWAS signal in the MS4A locus for AD risk and indicate that TREM2 may be involved in AD pathogenesis not only in TREM2 risk-variant carriers but also in those with sporadic disease.
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| 30. |
- Dewan, Ramita, et al.
(författare)
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Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
- 2021
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Ingår i: Neuron. - : Elsevier BV. - 1097-4199 .- 0896-6273. ; 109:3
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Tidskriftsartikel (refereegranskat)abstract
- We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.
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| 31. |
- Dimitrijevic Carlsson, Alexandra, 1966-, et al.
(författare)
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Juvenile idiopathic arthritis and the temporomandibular joint : a case-control study of magnetic resonance imaging findings in relation to clinical and psychosocial factors
- 2023
-
Ingår i: European Journal of Paediatric Dentistry. - : Società Italiana di Odontoiatria Infantile. - 1591-996X .- 2035-648X. ; 24:1, s. 69-76
-
Tidskriftsartikel (refereegranskat)abstract
- AimIn juvenile idiopathic arthritis (JIA), the temporomandibular joint (TMJ) is a particularly challenging joint to assess both clinically and with imaging. The aim of this article is to investigate TMJ magnetic resonance imaging (MRI) findings in relation to clinical and psychosocial factors in patients with JIA and healthy individuals related to TMJ arthritis in JIA.Material and methods In total, 45 patients (6–16 years) with JIA and 16 healthy age- and sex-matched controls were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered questionnaires about psychosocial factors (pain intensity, pain-related disability, depression, stress, catastrophising, pain locations, and jaw function) and underwent bilateral MRI of the TMJ.ResultsThere were no significant differences between JIA patients and healthy individuals in any of the TMJ MRI findings. Moderate/severe changes among JIA patients were found only for effusion, synovial thickening, condylar flattening, and erosion, with no moderate/severe changes in healthy individuals. In JIA patients, orofacial pain intensity was related to TMJ bone marrow oedema, and pain in jaw muscles during jaw function was related to TMJ bone marrow oedema and erosion. There were no significant correlations between psychosocial aspects and MRI findings.ConclusionsThis study indicates a substantial overlap of TMJ MRI findings in both the inflammatory domain and the damage domain between JIA patients and healthy individuals. In JIA patients, the inflammatory MRI sign of bone marrow oedema seems to influence orofacial pain intensity.
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| 32. |
- Dimitrijevic Carlsson, Alexandra, 1966-, et al.
(författare)
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Parotid saliva and blood biomarkers in juvenile idiopathic arthritis in relation to temporomandibular joint magnetic resonance imaging findings
- 2024
-
Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 0305-182X.
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundJuvenile idiopathic arthritis (JIA) often affects the temporomandibular joint (TMJ) caused by an abnormal immune system that includes overactive inflammatory processes. Salivary biomarkers may be a powerful tool that can help establishing diagnosis, prognosis and monitor disease progress.ObjectiveThe objective was to investigate biomarkers in parotid saliva and blood plasma in relation to temporomandibular joint (TMJ) magnetic resonance imaging (MRI) findings in patients with JIA and healthy individuals.MethodsForty-five children aged 6 to 16 years with JIA and 16 healthy age- and sex-matched controls were included. Unstimulated parotid saliva samples and venous blood were collected. Biochemical analyses were performed for the cytokine biomarkers. The participants underwent MR imaging of the TMJs, where changes in the inflammatory and the damage domains were assessed.ResultsIn the JIA patients, lower concentrations of IL-6R and gp130 were found in parotid saliva than in plasma. Higher concentrations of IL-6 were found in parotid saliva than in plasma. IL-6, IL-6R and gp130 in parotid saliva explained the presence of bone marrow oedema and effusion in the JIA patients.ConclusionsThis study suggests that the IL-6 family in parotid saliva is associated with TMJ bone marrow oedema and effusion in patients with JIA, suggesting that IL-6 has promising properties as a parotid saliva biomarker for TMJ inflammatory activity. image
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| 33. |
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| 34. |
- Dimitrijevic Carlsson, Alexandra, 1966-
(författare)
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The Temporomandibular Joint in Juvenile Idiopathic Arthritis : Psychosocial, clinical, imaging and parotid saliva biomarkers
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The disease can affect the temporomandibular joint (TMJ) and cause orofacial growth disturbances, pain, and jaw dysfunction. TMJ arthritis is often asymptomatic and therefore a challenging joint to diagnose. Clinical assessment of the TMJ is hampered by the low sensitivity and specificity of joint pain and the absence of physical findings early in the disease process. More specific methods are therefore needed for diagnosing TMJ arthritis. Saliva and blood are promising as diagnostic fluids for various diseases. Also, adolescents with chronic pain report high rates of psychosocial stress. Psychosocial stress may also be involved in JIA as a trigger and maintaining factor of the disease. Aim: The main aim of this thesis research was to investigate the relation between clinical variables, psychosocial factors, MRI findings, and inflammatory biomarkers in saliva and blood in relation to TMJ involvement in JIA. The secondary aim was to investigate the relation between stress and change in stress over time in comparison with orofacial pain, psychosocial factors, and jaw function in JIA patients. Methods: This was a cross-sectional case-control study and a longitudinal cohort study. Forty-five patients (6-16 years old) with JIA and 16 healthy age- and sex-matched healthy individuals were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The study subjects completed questionnaires regarding psychosocial factors and underwent bilateral MRI of their TMJs. Unstimulated parotid saliva and venous blood samples were collected. Biochemical analyses were performed using a multiplex platform electrochemiluminescence assay from Meso Scale Discovery (MSD) for measuring cytokine concentrations in saliva and blood. A two-year prospective follow-up study was performed in 40 JIA patients from our original baseline study. The JIA patients underwent the same clinical examination and completed the same questionnaires regarding psychosocial factors as in the baseline studies. Results: The JIA patients with orofacial pain had higher degrees of stress, depression, catastrophizing, and jaw dysfunction than did those JIA patients without such pain. These factors were also associated with orofacial pain intensity. Additionally, patients with orofacial pain had higher systemic inflammatory activity. In the two-year follow-up study, we observed that change in stress was associated with changes in catastrophizing, psychological distress, as well as limitations in both general and jaw functions. Regarding TMJ MRI findings, there were no significant differences between JIA patients and healthy individuals in either the inflammatory or damage domain. Moderate/severe TMJ changes in the inflammatory and damage domains were, however, only found in the JIA patients. Among JIA patients, orofacial pain intensity was correlated to TMJ bone marrow edema, and pain in jaw muscles during jaw function was related to both TMJ bone marrow edema and erosion. JIA patients had lower concentrations of interleukin receptor 6 (IL-6R) and glycoprotein 130 (gp130) in parotid saliva than in plasma. Higher concentrations of IL-6 were found in parotid saliva than in plasma. The members of the interleukin-6 family (i.e., IL-6, IL-6R, and gp130) in parotid saliva were found to be explanatory factors for the presence of bone marrow edema and effusion in the JIA patients. Conclusions: Orofacial pain in patients with JIA is associated with stress, psychological distress, jaw dysfunction, and loss of daily living activities. Pain intensity seems to be the major aspect related to these factors. Increased disease activity with more joint involvement seems to be an important factor contributing to orofacial pain in JIA. Myalgia, in addition to arthritis, seems to be an important source of orofacial pain in these patients. Maintaining a low stress level in JIA patients seems to be crucial, as an increase in stress level over a two-year period appears to negatively impact both jaw function as well as psychosocial distress and catastrophizing. There was an overlap of TMJ MRI findings regarding signs of inflammatory and bone tissue changes between JIA patients and healthy individuals. Among, JIA patients, the presence of inflammatory MRI signs, and bone marrow edema seems to worsen orofacial pain intensity. The IL-6 family in parotid saliva is associated with TMJ bone marrow edema and effusion in patients with JIA, suggesting that IL-6 has promising properties as a parotid saliva biomarker of TMJ inflammatory activity. In addition there seems to be local production of the IL-6 family in the parotid gland in JIA patients and healthy individuals. However, parotid saliva does not seem to reflect the plasma content in terms of the investigated biomarkers in JIA.
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| 35. |
- Dimitrijevic Carlsson, Alexandra, 1966-, et al.
(författare)
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Unstimulated Parotid Saliva Sampling in Juvenile Idiopathic Arthritis and Healthy Controls : A Proof-of-Concept Study on Biomarkers
- 2020
-
Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- The aims of this proof-of-concept study were to develop a collecting method for unstimulated parotid saliva in juvenile idiopathic arthritis (JIA) patients and healthy children and to investigate if inflammatory biomarkers could be detected in these samples. Forty-five children with JIA (median age of 12 years and 25th-75th percentile of 10-15 years; 33 girls and 12 boys) and 16 healthy children as controls (median age of 13 years and 25-75th percentile of 10-13 years; 11 girls and 5 boys) were enrolled in this study. Unstimulated parotid saliva was collected with a modified Carlson-Crittenden collector. The salivary flow rate and salivary concentrations of total protein and inflammatory mediators were assessed. The Meso Scale Discovery electrochemiluminescence immunoassay was used for analyzing protein concentrations and the inflammatory biomarkers. Sufficient parotid saliva volumes to be analyzed could be collected with the collection device. JIA patients had a lower sampling saliva volume (p = 0.008) and saliva flow rate (p = 0.039) than controls. The total protein concentrations and inflammatory biomarkers were measured in the last six healthy subjects. The median protein concentration was 1312 mu g/mL (25th percentile: 844 mu g/mL and 75th percentile: 2062 mu g/mL; n = 6) and quantifiable concentrations of 39 inflammatory proteins could be assessed in these samples. In conclusion, this study indicates that the saliva sampling method, as used in the present study, is able to collect sufficient sample volumes in children, and that it is possible to analyze various inflammatory biomarkers in the collected saliva.
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| 36. |
- Dwibedi, Chinmay Kumar, et al.
(författare)
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Biological amplification of low frequency mutations unravels laboratory culture history of the bio-threat agent Francisella tularensis
- 2020
-
Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Challenges of investigating a suspected bio attack include establishing if microorganisms have been cultured to produce attack material and to identify their source. Addressing both issues, we have investigated genetic variations that emerge during laboratory culturing of the bacterial pathogen Francisella tularensis. Key aims were to identify genetic variations that are characteristic of laboratory culturing and explore the possibility of using biological amplification to identify genetic variation present at exceedingly low frequencies in a source sample. We used parallel serial passage experiments and high-throughput sequencing of F. tularensis to explore the genetic variation. We found that during early laboratory culture passages of F. tularensis, gene duplications emerged in the pathogen genome followed by single-nucleotide polymorphisms in genes for bacterial capsule synthesis. Based on a biological enrichment scheme and the use of high-throughput sequencing, we identified genetic variation that likely pre-existed in a source sample. The results support that capsule synthesis gene mutations are common during laboratory culture, and that a biological amplification strategy is useful for linking a F. tularensis sample to a specific laboratory variant among many highly similar variants.
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| 37. |
- Ekstrand, Matias, et al.
(författare)
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Depletion of ATP and glucose in advanced human atherosclerotic plaques
- 2017
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Ingår i: PLoS One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Severe hypoxia develops close to the necrotic core of advanced human atherosclerotic plaques, but the energy metabolic consequences of this hypoxia are not known. In animal models, plaque hypoxia is also associated with depletion of glucose and ATP. ATP depletion may impair healing of plaques and promote necrotic core expansion. To investigate if ATP depletion is present in human plaques, we analyzed the distribution of energy metabolites (ATP, glucose, glycogen and lactate) in intermediate and advanced human plaques.Snap frozen carotid endarterectomies from 6 symptomatic patients were analyzed. Each endarterectomy included a large plaque ranging from the common carotid artery (CCA) to the internal carotid artery (ICA). ATP, glucose, and glycogen concentrations were lower in advanced (ICA) compared to intermediate plaques (CCA), whereas lactate concentrations were higher. The lowest concentrations of ATP, glucose and glycogen were detected in the perinecrotic zone of advanced plaques.Our study demonstrates severe ATP depletion and glucose deficiency in the perinecrotic zone of human advanced atherosclerotic plaques. ATP depletion may impair healing of plaques and promote disease progression.
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| 38. |
- Frodigh, Magnus, et al.
(författare)
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Future-generation wireless networks
- 2001
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Ingår i: IEEE personal communications. - : Institute of Electrical and Electronics Engineers (IEEE). - 1070-9916 .- 1558-0652. ; 8:5, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- Starting with today's 3G standards, future-generation wireless networks are discussed. Two complementing major trends are identified: seamless roaming between different air interfaces, leading to the Always Best Connected concept, and the continuous development of the current third-generation standards. The evolution of WCDMA toward high-speed downlink packet access, aiming for peak rates in the order of 8-10 Mb/s, is described as an example of air-interface evolution., Fourth-generation technologies such as ad hoc networking and multihop networks, still at the research level, are discussed and their impact on wireless communication systems addressed.
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| 39. |
- Hatschek, Thomas, et al.
(författare)
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Neoadjuvant Trastuzumab, Pertuzumab, and Docetaxel vs Trastuzumab Emtansine in Patients With ERBB2-Positive Breast Cancer A Phase 2 Randomized Clinical Trial
- 2021
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 7:9, s. 1360-1367
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Trastuzumab emtansine (T-DM1) is presently approved for treatment of advanced breast cancer and after incomplete response to neoadjuvant therapy, but the potential of T-DM1 as monotherapy is so far unknown.OBJECTIVE: To assess pathologic complete response (pCR) to standard neoadjuvant therapy of combination docetaxel, trastuzumab, and pertuzumab (DTP) vs T-DM1 monotherapy in patients with ERBB2 (formerly HER2)-positive breast cancer.DESIGN, SETTING, AND PARTICIPANTS: This randomized phase 2 trial, conducted at 9 sites in Sweden, enrolled 202 patients between December 1, 2014, and October 31, 2018. Participants were 18 years or older, with ERBB2-positive tumors larger than 20 mm and/or verified lymph node metastases. Analysis was performed on an intention-to-treat basis.INTERVENTIONS: Patients were randomized to receive 6 cycles of DTP (standard group) or T-DM1 (investigational group). Crossover was recommended at lack of response or occurrence of intolerable toxic effects. Assessment with fluorine 18-labeled fluorodeoxyglucose (F-18-FDG) positron emission tomography combined with computed tomography (PET-CT) was performed at baseline and after 2 and 6 treatment cycles.MAIN OUTCOME AND MEASURES: Pathologic complete response, defined as ypT0 or Tis ypN0. Secondary end points were clinical and radiologic objective response; event-free survival, invasive disease-free survival, distant disease-free survival, and overall survival; safety; health-related quality of life (HRQoL); functional and biological tumor characteristics; and frequency of breast-conserving surgery.RESULTS: Overall, 202 patients were randomized; 197 (99 women in the standard group [median age, 51 years (range, 26-73 years)] and 98 women in the investigational group [median age, 53 years (range, 28-74 years)]) were evaluable for the primary end point. Pathologic complete response was achieved in 45 patients in the standard group (45.5%; 95% CI 35.4%-55.8%) and 43 patients in the investigational group (43.9%; 95% CI 33.9%-54.3%). The difference was not statistically significant (P = .82). In a subgroup analysis, the pCR rate was higher in hormone receptor-negative tumors than in hormone receptor-positive tumors in both treatment groups (45 of 72 [62.5%] vs 45 of 125 [36.0%]). Three patients in the T-DM1 group experienced progression during therapy. In an exploratory analysis, tumor-infiltrating lymphocytes at 10% or more (median) estimated pCR significantly (odds ratio, 2.76; 95% CI, 1.42-5.36; P = .003). Response evaluation with F-18-FDG PET-CT revealed a relative decrease of maximum standardized uptake value by more than 31.3% (median) was associated with pCR (odds ratio, 6.67, 95% CI, 2.38-20.00; P < .001).CONCLUSIONS AND RELEVANCE: In this study, treatment with standard neoadjuvant combination DTP was equal to T-DM1.
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| 40. |
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| 41. |
- Heslegrave, Amanda, et al.
(författare)
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Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer's disease.
- 2016
-
Ingår i: Molecular neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- The discovery that heterozygous missense mutations in the gene encoding triggering receptor expressed on myeloid cells 2 (TREM2) are risk factors for Alzheimer's disease (AD), with only the apolipoprotein E (APOE) ε4 gene allele conferring a higher risk, has led to increased interest in immune biology in the brain. TREM2 is expressed on microglia, the resident immune cells of the brain and has been linked to phagocytotic clearance of amyloid β (Aβ) plaques. Soluble TREM2 (sTREM2) has previously been measured in cerebrospinal fluid (CSF) by ELISA but in our hands commercial kits have proved unreliable, suggesting that other methods may be required. We developed a mass spectrometry method using selected reaction monitoring for the presence of a TREM2 peptide, which can be used to quantify levels of sTREM2 in CSF.
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| 42. |
- Horvath, Istvan, et al.
(författare)
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Pro-inflammatory S100A9 Protein as a Robust Biomarker Differentiating Early Stages of Cognitive Impairment in Alzheimer's Disease
- 2016
-
Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 7:1, s. 34-39
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Tidskriftsartikel (refereegranskat)abstract
- Pro-inflammatory protein S100A9 was established as a biomarker of dementia progression and compared with others such as Aβ1-42 and tau-proteins. CSF samples from 104 stringently diagnosed individuals divided into five subgroups were analyzed, including nondemented controls, stable mild cognitive impairment (SMCI), mild cognitive impairment due to Alzheimer's disease (MCI-AD), Alzheimer's disease (AD), and vascular dementia (VaD) patients. ELISA, dot-blotting, and electrochemical impedance spectroscopy were used as research methods. The S100A9 and Aβ1-42 levels correlated with each other: their CSF content decreased already at the SMCI stage and declined further under MCI-AD, AD, and VaD conditions. Immunohistochemical analysis also revealed involvement of both Aβ1-42 and S100A9 in the amyloid-neuroinflammatory cascade already during SMCI. Tau proteins were not yet altered in SMCI; however their contents increased during MCI-AD and AD, diagnosing later dementia stages. Thus, four biomarkers together, reflecting different underlying pathological causes, can accurately differentiate dementia progression and also distinguish AD from VaD.
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| 43. |
- Hägg Samuelsson, Ulrika, 1973, et al.
(författare)
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Gene expression profile and aortic vessel distensibility in voluntarily exercised spontaneously hypertensive rats: potential role of heat shock proteins
- 2005
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Ingår i: Physiol Genomics. - 1531-2267 .- 1094-8341. ; 22:3, s. 319-26
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Tidskriftsartikel (refereegranskat)abstract
- Physical exercise is considered to be beneficial for cardiovascular health. Nevertheless, the underlying specific molecular mechanisms still remain unexplored. In this study, we aimed to investigate the effects of voluntary exercise on vascular mechanical properties and gene regulation patterns in spontaneously hypertensive rats. By using ultrasound biomicroscopy in an ex vivo perfusion chamber, we studied the distensibility of the thoracic aorta. Furthermore, exercise-induced gene regulation was studied in aortae, using microarray analysis and validated with real-time PCR. We found that distensibility was significantly improved in aortas from exercising compared with control rats (P < 0.0001). Exercising rats demonstrated a striking pattern of coordinated downregulation of genes belonging to the heat shock protein family. In conclusion, voluntary exercise leads to improved vessel wall distensibility and reduced gene expression of heat shock protein 60 and 70, which may indicate decreased oxidative stress in the aortic vascular wall.
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| 44. |
- Johansson, Anders, 1966-, et al.
(författare)
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Multiple-locus variable-number tandem repeat analysis for typing of Staphylococcus epidermidis.
- 2006
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 44:1, s. 260-5
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Tidskriftsartikel (refereegranskat)abstract
- We applied a high-resolution PCR-based typing method, multiple-locus variable-number tandem repeat analysis (MLVA), for discrimination of 30 multidrug-resistant clinical isolates of Staphylococcus epidermidis. The results of MLVA were congruent with results obtained by pulsed-field gel electrophoresis (PFGE). MLVA generated discrete character data, and its discriminatory capacity was comparable to that of PFGE.
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| 45. |
- Johansson, Mona, et al.
(författare)
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Platelet adhesion in type 2 diabetes : impact of plasma albumin and mean platelet volume.
- 2021
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Ingår i: Thrombosis Journal. - : BioMed Central (BMC). - 1477-9560. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Altered mean platelet volume (MPV) and plasma albumin has been reported in type 2 diabetes (T2D). MPV is suggested to predict cardiovascular risk but there is a lack of evidence for associations between MPV and platelet adhesion. Plasma albumin and magnesium are other factors reported to influence thrombotic risk. The objectives of this study were to assess the association between platelet adhesion and plasma factors with a potential role to affect platelet activation.METHODS: Blood was collected from 60 T2D patients and 60 healthy controls. Platelet adhesion to different protein surfaces induced by various soluble activators were measured in microplates. MPV, albumin and magnesium were analysed together with additional routine tests.RESULTS: Despite normal levels, plasma albumin significantly correlated with adhesion of T2D platelets but not with controls. There was a significant association between MPV and platelet adhesion in both groups, but association was smaller in T2D. Levels of glucose, HbA1c or magnesium did not correlate with platelet adhesion.CONCLUSIONS: Plasma albumin was associated with platelet adhesion in T2D suggesting that albumin may be a factor to consider upon cardiovascular risk assessment. MPV was more associated with the level of platelet adhesion in healthy individuals than in well-controlled T2D patients.
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| 46. |
- Johansson, Mona, et al.
(författare)
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Weak relationship between ionized and total magnesium in serum of patients requiring magnesium status
- 2007
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Ingår i: Biological Trace Element Research. - 0163-4984 .- 1559-0720. ; 115:1, s. 13-21
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Tidskriftsartikel (refereegranskat)abstract
- Measurement and monitoring of magnesium (Mg) are important to prevent the development of serious and potentially fatal complications in critically ill patients. Although ion-selective electrodes are available and earlier reports suggest that free ionized magnesium (iMg2+) is the most useful test to estimate Mg status, most clinical laboratories still only measure total Mg. To compare the relationship among iMg2+, total Mg, and albumin in serum, samples were collected from 48 consecutive patients admitted to an intensive care unit or a primary health center. The mean serum level of iMg2+ in 44 patients was 0.53 mmol/L, the total Mg was 0.96 mmol/L, and the albumin was 34.93 g/L. The correlation between iMg2+ and total Mg in serum was r=0.585, the correlation between iMg2+ and albumin in serum was r=378, and the correlation between total Mg and albumin in serum was r=0.340. The mean percent iMg2+ in relation to total Mg in serum was calculated to be 55% in the patient samples. The important level of biologically active iMg2+ was not reflected upon analysis of total Mg in 25% of consecutive patients. This report shows that the correlation of iMg2+ and total Mg is weak, not only in critically ill patients but also in patients in whom Mg status is inquired as a whole.
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| 47. |
- Johansson, Olof, et al.
(författare)
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Effectiveness of guided internet-delivered cognitive behavior therapy for depression in routine psychiatry : A randomized controlled trial
- 2019
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Ingår i: Internet Interventions. - : Elsevier BV. - 2214-7829. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Depression is one of the most common health problems worldwide but is often undertreated. Internet-delivered cognitive behavioral therapy(ICBT) appears to be an effective treatment option, with the potential to reach a larger proportion of individuals suffering from depression. While many studies have examined the efficacy of ICBT for depression in randomized controlled trials, fewer have focused on the effectiveness of ICBT when used as an integral part of routine health care. In this study the effectiveness of an 8-week ICBT program was examined when delivered in a routine psychiatric setting. A total of 108 patients were referred and 54 were then included and randomized to either ICBT or a waitlist control condition. The sample had a lower education level and a higher proportion of individuals were on sick leave than comparable previous efficacy trials of ICBT for depression conducted in Sweden. Measures assessing depression, anxiety and psychiatric symptoms were administered before and after treatment, follow up was performed at 6- and 12 months after treatment had ended. ICBT resulted in significant reductions of depressive symptoms in the treatment group when compared to a waitlist control group with a large effect size (Cohen's d = 1.6). Treatment gains were maintained at 6- and 12 months after the treatment had ended. In terms of clinical significance, 58% of the sample had improved or recovered after treatment. The study was small, and patients received general psychiatric care after the ICBT treatment had ended which limits the implications. We conclude that ICBT appears to be an effective treatment for depression when delivered as an integral part of routine psychiatric care.
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| 48. |
- Johansson, Per Magnus, 1950, et al.
(författare)
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Arkitektliv : Intervju med Gert Wingårdh
- 2011
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Ingår i: Arche. - 2000-7817. ; :36-37
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Interview with Architect Gert Wingårdh made by Per Magnus Johansson & Johan Linton. 78 pages with illustrations.
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| 49. |
- Johansson, Per Magnus, 1950, et al.
(författare)
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Arkitektliv
- 2011
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Ingår i: Arche. - 2000-7817.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Interview with Architect Gert Wingårdh made by Per Magnus Johansson & Johan Linton. 78 pages with illustrations.
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| 50. |
- Johansson, Per Magnus, 1950, et al.
(författare)
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Håkan Lindqvist : Arkitekt och forskare
- 2011
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Ingår i: Arche. - 2000-7817. ; :36-37
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction of the Architect and researcher Håkan Lindqvist and of a special section, 58 pages long, on the Gothenburg architect Hans Hedlund (1855-1931), written mainly by Lindqvist, but also by Prof Claes Caldenby.
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