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- Lind, Anne-Li, et al.
(författare)
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Affinity Proteomics Applied to Patient CSF Identifies Protein Profiles Associated with Neuropathic Pain and Fibromyalgia
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Today, there are no biological tests on which to base pain diagnoses, treatment choices or to understand the biological processes underlying and accompanying chronic pain for the individual pain patient. Relevant biological markers would greatly aid in diagnosis and treatment of patients with chronic pain. Our study aimed to find proteins in CSF associated with fibromyalgia and neuropathic pain, two common and poorly understood chronic pain conditions.Methods: We have performed CSF protein profiling of 55 proteins using a 100-plex antibody suspension bead array. We collected, analyzed and compared CSF samples from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery and n=11 for verification), 40 patients with fibromyalgia and 135 controls without neurological disease from two different populations.Results: We found significant differences in CSF protein levels between patients and controls (p<0.05). Among these proteins, Apolipoprotein C1 (APOC1) was found to be increased in CSF of neuropathic pain patients compared to controls and there was a non-significant trend for increased levels also in fibromyalgia patient CSF. Ectonucleotide pyrophosphatase (ENPP2, Autotaxin) was increased in the CSF of fibromyalgia patients compared to all other groups including neuropathic pain patients. Multivariate analysis revealed partially overlapping and partially distinct CSF profiles in neuropathic pain patients compared with fibromyalgia and controls for several other proteins including angiotensinogen (AGT), prostaglandin-H2 D-isomerase (PTGDS), neurexin-1 (NRXN1), superoxide dismutase 1 (SOD1) and superoxide dismutase 3 (SOD3).Conclusions: Our results, suggest that the CSF protein profiles of neuropathic pain and fibromyalgia patients may be different from each other and from those of controls. CSF levels of APOC1, ENPP2, AGT, PTGDS, NRXN1, SOD1 and SOD3 should be further investigated for their potential to serve as biomarkers of different kinds of pain pathophysiology.
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- Elfström, Peter, 1974-, et al.
(författare)
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Hematopoietic cancer including lymphoma in celiac disease according to Marsh criteria 0-3
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Celiac disease (CD) is associated with an increased risk of lymphoma, but it is unknown if borderline mucosal damage and latent CD are risk factors for lymphoma.Methods: We examined the risk of hematopoietic cancer in a nationwide population–based cohort of 28,800 individuals with biopsy-verified CD (villous atrophy, Marsh 3), 12,663 individuals with small intestinal inflammation (Marsh 1+2), and 3,551 with latent CD (positive antiendomysial, tissue transglutaminase or antigliadin test but normal mucosa on biopsy). The study participants were identified through all pathology departments (n=28) in Sweden and were biopsied in 1969-2006 (median: 1998). Cox regression estimated the hazard ratio (HR) for hematopoietic malignancies.Results: While biopsy-verified CD and intestinal inflammation were both statistically significantly associated with lymphoma (CD: HR = 3.18; 95% CI = 2.63-3.83; inflammation: 1.66; 1.28-2.17), latent CD was not (1.04; 0.44-2.43). CD was associated with both non-Hodgkin’s (NHL) and Hodgkin’s lymphoma (HL) (4.81; 3.81-6.07 and 4.39; 2.59-7.45 respectively). Risk estimates for NHL and HL were lower in inflammation (1.65; 1.15-2.38 and 1.48; 0.60-3.62 respectively) and latent CD (1.79; 0.74-4.34 and 1.08; 0.13-9.00 respectively). No increased risk of lymphoma was seen in children with a small intestinal biopsy. This study found no association between leukemia and small intestinal pathology.Conclusion: CD is associated with an increased risk of lymphoma. This risk increase was also seen in individuals with small intestinal inflammation. Latent CD is not associated with lymphoma of any kind, and positive CD serology alone cannot be used to predict future risk of lymphoma.
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- Kaltsouni, Elisavet, et al.
(författare)
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Selective progesterone receptor modulation and brain activity at rest in patients with premenstrual dysphoric disorder
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Ovarian hormones have been indicated to impact brain connectivity and mood. However, there is no consistent evidence on hormone-dependent functional connectivity and mental health. Alterations in resting state networks have been suggested as markers of affective disorders, but only preliminary evidence is provided on premenstrual dysphoric disorder, in which symptoms occur upon fluctuations of ovarian hormones. Recently, three-month low-dose selective progesterone receptor modulator (SPRM) administration has been associated with symptom relief and altered task-based brain reactivity during a reactive aggression condition. The present study sought to investigate the effect of this treatment on resting state functional connectivity (rs-FC) in patients with PMDD. Seed-based analyses were conducted, including including seeds from the classic resting state networks along with the functional cluster affected by SPRM treatment. Within previously identified networks related with emotional processing, rs-FC was compared between individuals with PMDD during the symptomatic luteal phase before randomization to treatment or placebo and during the end of the last treatment cycle. Seed-based rs-FC analyses yielded significant treatment by time effects on rs-FC between the left posterior superior temporal gyrus and the right insula cortex, between the posterior cerebellum and the left temporal pole, and between the right lateral visual network and left superior frontal gyrus. Visuo-frontal luteal phase connectivity decreased for the SPRM group and was positively correlated with changes in mood symptom severity in the placebo group. Cerebellar and temporal connectivity increased for the SPRM treatment group, while temporo-insular connectivity decreased and was positively correlated with cortisol levels. These findings indicate that SPRM treatment influenced rs-FC, which could be a relevant mechanism behind symptom alleviation.
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- Pourhamidi, Kaveh, et al.
(författare)
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Heat shock protein 27 concentrations are lower in patientswith type 1 diabetes mellitus than in healthy controls andcorrelates with large nerve fibre dysfunction
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective Heat shock protein 27 (HSP27) may contribute to the survival of neurons. Our aims were to study whether HSP27 concentrations differ between individuals with and without type 1 diabetes, and evaluate the relationship between the progression of peripheral nerve dysfunction and HSP27 concentrations.Research Design and Methods Type 1 diabetes patients (n=27, 41% women; mean age 41±8 years) were recruited in 1992 with a follow-up in 2005; serum HSP27 concentrations were determined in baseline and follow-up samples and compared to non-diabetic controls (n=397, 34% women; mean age 43±14 years). The type 1 diabetes patients underwent nerve conduction studies and thermal and vibration perception threshold tests at baseline and at follow-up. Reference data was used to standardise results for age, height and sex by calculating the Z-scores. Delta changes in HSP27 (follow-up HSP27 – baseline HSP27) and small and large nerve fibre function were used for correlation analyses.Results Type 1 diabetes patients had lower HSP27 concentrations at baseline (mean HSP27547 pg/ml, 95% CI 421, 711) and at follow-up (mean HSP27 538 pg/ml, 95% CI 417,693) compared to healthy controls (mean HSP27 785 pg/ml, 95% CI 732, 842; p<0.05 for both comparisons). Deteriorating large nerve fibre function correlated with delta HSP27 concentrations in type 1 diabetes (r=0.50, p=0.01).Conclusions Patients with type 1 diabetes had lower HSP27 concentrations than non-diabetic controls and progression of large nerve fibre dysfunction correlated with decreasing HSP27 concentrations during the follow-up period. This could be indicative ofinsufficient neuroprotection in type 1 diabetes.
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- Hagnelius, Nils-Olof, 1953-, et al.
(författare)
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Fibrinolysis and von Willebrand factor in Alzheimer's disease and vascular dementia : a case-referent study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The importance of vascular risk factors for Alzheimer’s disease (AD) is not settled. Our aim was to compare patients with AD or vascular dementia (VaD) with non-demented subjects with regard to endothelial derived fibrinolytic and hemostatic factors.Materials and methods: In a cross-sectional mono-center case-referent study in Örebro, Sweden, we consecutively included 95 patients with AD and 55 with VaD and 154 non-demented active seniors (AS). Plasma biomarkers including the endothelial derived fibrinolytic factors: mass concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), tPA/PAI-1 complex and von Willebrand factor (vWF), as well as clinical data were analyzed.Results: None of the endothelial derived fibrinolytic markers or vWF differed between AD vs. VaD. In comparison with the AS group, tPA was higher in AD (p=0.001) and VaD (p=0.023) but its inhibitor, PAI-1 mass concentration did not differ significantly; tPA/PAI-1 complex was higher in both VaD (p=0.038) and AD (p=0.005). vWF concentration was lower in the AS group (p<0.001) than in both dementia groups.Conclusion: Thus, endothelial derived fibrinolytic factors, tPA/PAI-1 complex and vWF, discriminated between the reference group of non-demented elderly and the AD and VaD groups, but not between AD and VaD. This suggests similar disturbances for endothelial derived fibrinolytic and hemostatic factors among AD and VaD patients and may reflect shared vascular pathophysiological mechanisms in the dementias.
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- Hagnelius, Nils-Olof, 1953-, et al.
(författare)
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High homocysteine and methylmalonate among demented and non-demented elderly receiving vitamin-B12 prescription and home help service
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background & Aims: Total homocysteine (tHcy) has been suggested as a dementia risk factor. Our aim was to investigate potential differences in tHcy and its determinants (mainly Serum-B12 and Serum-folate) in relation dementia. We examined the effect of vitamin-B12 prescription, whether a family history of dementia, or the need for home help service might have influence on tHcy.Methods: A cross sectional monocenter study comprising 926 consecutive subjects attending our Memory Care Unit.Results: Demented subjects being prescribed vitamin-B12 had higher Serum-B12 (p =0.025) but also higher tHcy (p =<0.001) and S-methylmalonate (p =0.032), and lower Serum-folate (p<0.001) than those who did not receive B12 prescriptions. tHcy levels were higher in subjects in need of home help service (non-dementia: p= 0.007), this group also had lower S-albumin (dementia: p<0.001; non-dementia: p=0.004). In multivariate logistic regression analysis with diagnosis of dementia as outcome, both vitamin-B12 prescriptions, family history of dementia, and existent home help service, predicted dementia (p=0.037; 0.044; 0.002 respectively).Conclusion: Elderly subjects on vitamin-B12 prescription appear to have unmet needs of nutritional support, causing elevated homocysteine levels. The home help service should pay a closer attention to nutritional aspects and drug compliance among geriatric patients.
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| 9. |
- Löfgren, Magnus, 1979-, et al.
(författare)
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Chronic subordination stress augments combined progesterone and estradiol withdrawal behavior
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Exposure to stress is a risk factor for developing pre-menstrual syndrome (PMS) and pre-menstrual dysphoric disorder (PMDD), and stress enhances the anxiogenic effect of female sex steroids in animals. This study examines the interaction between chronic subordination stress and withdrawal from progesterone (P4) and estradiol (E2) (PEWD) in producing behaviors analogous to anxiety and irritability in rats. At the start of the experiment, male Wistar rats were housed in triads consisting of one younger rat (~35 days) and two older rats (~50 days). The housing condition was aimed at producing chronic subordination stress in the younger animals. Chronic subordination stress was assessed by the elevated plus maze (EPM) and by corticosterone (CORT) analysis. A triad of three 35-day-old rats was used as age control. Social rank within the triads was determined using a food competition test (FCT) and the tube test (TT). The younger rats (subordinate) and the dominant rats were assigned to 10 days of treatment with 5 mg/kg progesterone combined with 10 µg/kg 17β estradiol. Twenty-four hours after the last injection, the subordinate and dominant animals were tested in the open-field test (OFT) and in the intruder test (IT). The IT consists of a 10-minute exposure to 3 unfamiliar rats. Chronic subordination stress reduced EPM open-arm time and altered the CORT response. It also made the subordinate animals more vulnerable to PEWD. The effects were increased locomotion in the OFT, increased defensive burying, and increased social anxiety in the intruder test (IT). Dominant animals did not react to PEWD. Thus, chronic subordination stress augments PEWD.
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- Lundh, Torbjörn, 1965, et al.
(författare)
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Torque Devices
- 2018
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Torque devices for navigating a guidewire through a body lumen are disclosed. The devices have a variable speed transmission design, including at least a first transmission region along a first position of the device, and a second transmission region along a second position of the device. The first and second transmission regions have different diameters, thereby allowing rotational control of the guidewire between at least two different stroke angles.
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