| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Jungedal, R, et al.
(författare)
-
Prevalence of anti-drug antibodies against interferon beta has decreased since routine analysis of neutralizing antibodies became clinical practice
- 2012
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 18:12, s. 1775-1781
-
Tidskriftsartikel (refereegranskat)abstract
- Neutralizing antibodies (NAbs) against interferon beta (IFNβ) lead to loss of treatment efficacy in multiple sclerosis patients. The seroprevalence of NAbs in multiple sclerosis patients treated with IFNβ during 2003–2004 was 32% in a cross-sectional analysis of routine data. Objectives: The aim of this study was to investigate whether the seroprevalence of NAbs, the levels of NAb titres and the IFNβ preparations used for treatment of multiple sclerosis patients had changed in 2009–2010. Methods: This study included 1296 patients, analysed for NAbs with the myxovirus resistance protein A gene expression assay in 2009–2010. Results: The seroprevalence of NAbs had decreased to 19% in 2009–2010, which is significantly lower compared with the previous study in 2003–2004 ( p<0.0001). This decrease was attributed to the IFNβ-1a preparations only, not to IFNβ-1b. The frequency of patients with high positive titres decreased the most, from 16% to 7% ( p<0.0001). Conclusions: NAb seroprevalence has decreased since NAb monitoring became clinical practice in 2003, especially for patients with high NAb titres. This might be due to the stricter monitoring of NAb titres that prompt NAb positive patients to stop treatment, to preferential use of less immunogenic drugs and to alteration of drug formulations.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Burns, Tom R., et al.
(författare)
-
The Social Construction of Consciousness : Individual Selves, Self-Awareness, and Reflectivity. Part 2
- 1998
-
Ingår i: Journal of consciousness studies. - Thorverton. - 1355-8250 .- 2051-2201. ; 5:2, s. 166-184
-
Tidskriftsartikel (refereegranskat)abstract
- From a sociological and social psychological perspective, this paper outlines and develops a theoretical framework with which to define and analyse consciousness, emphasizing the role of language, collective representations, conceptions of self, and self-reflectivity in human conscious phenomena. The paper focuses on the social origins of conscious phenomena, on collective as well as individual levels. Part 1 of the paper (Burns and Engdahl, 1998a) dealt with collective consciousness. This second part analyses individual consciousness as arising in the context of a person experiencing herself as an object of collective representation and collective reflection and discourse. Individual consciousness is the outcome of processes of collective naming, classifying, monitoring, judging, reflecting on, and conducting discussions and discourses about, the individual herself. A participant learns in the collective context (in line with George Herbert Mead's earlier formulations) a naming and classification of herself (self-description and identity), of her judgments, actions, and predispositions. In acquiring a language and conceptual framework for this mode of activity -- along with experience and skills in reflective discussion -- she develops a capability of inner reflection and inner dialogue about self, which are characteristic features of individual consciousness. The analysis goes on to distinguish multiple modes of individual awareness and consciousness, distinguishing awareness from consciousness proper, and also identifying pre- and sub-conscious levels. This points up the complexity of the human mind, in part its elaboration through processes of social interaction and construction.
|
|
| 10. |
- Caporale, N., et al.
(författare)
-
From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
-
Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
|
|
| 11. |
- Engdahl, Cecilia, 1983, et al.
(författare)
-
Estrogen induces St6gal1 expression and increases IgG sialylation in mice and patients with rheumatoid arthritis: A potential explanation for the increased risk of rheumatoid arthritis in postmenopausal women
- 2018
-
Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Rheumatoid arthritis (RA) preferentially affects women, with the peak incidence coinciding with estrogen decrease in menopause. Estrogen (E2) may therefore have intrinsic immune-regulatory properties that vanish with menopause. Fc sialylation is a crucial factor determining the inflammatory effector function of antibodies. We therefore analyzed whether E2 affects immunoglobulin G (IgG) sialylation. Methods: Postmenopausal (ovariectomized) mice were immunized with ovalbumin and treated with E2 or vehicle. Total and ovalbumin-specific IgG concentrations, sialylation, and Fcγ receptor expression were analyzed. Postmenopausal women with RA receiving hormone replacement therapy, including E2, or no treatment were analyzed for IgG sialylation. Furthermore, effects of E2 on the expression of the sialylation enzyme β-galactoside α2,6-sialyltransferase 1 (St6Gal1) were studied in mouse and human antibody-producing cells. Results: E2 treatment significantly increased Fc sialylation of total and ovalbumin-specific IgG in postmenopausal mice. Furthermore, E2 led to increased expression of inhibitory Fcγ receptor IIb on bone marrow leukocytes. Treatment with E2 also increased St6Gal1 expression in mouse and human antibody-producing cells, providing a mechanistic explanation for the increase in IgG-Fc sialylation. In postmenopausal women with RA, treatment with E2 significantly increased the Fc sialylation of IgG. Conclusions: E2 induces anti-inflammatory effector functions in IgG by inducing St6Gal1 expression in antibody-producing cells and by increasing Fc sialylation. These observations provide a mechanistic explanation for the increased risk of RA in conditions with low estrogen levels such as menopause. © 2018 The Author(s).
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Engdahl, J, et al.
(författare)
-
The epidemiology of out-of-hospital "sudden" cardiac arrest
- 2002
-
Ingår i: Resuscitation. - : Elsevier Ireland Ltd. - 0300-9572 .- 1873-1570. ; 52:3, s. 235-245
-
Tidskriftsartikel (refereegranskat)abstract
- It is difficult to assemble data from an previous termout-of-hospital cardiac arrestnext term since there is often lack of objective information. The true incidence of previous termsudden cardiacnext term death previous termout-of-hospitalnext term is not known since far from all of these patients are attended by emergency medical services. The incidence of previous termout-of-hospital cardiac arrestnext term increases with age and is more common among men. Among patients who die, the probability of having a fatal event outside previous termhospitalnext term decreases with age; i. e. younger patients tend to more often die unexpectedly and outside previous termhospital.next term Among the different initial arrhythmias, ventricular fibrillation is the most common among patients with previous termcardiacnext term aetiology. The true distribution of initial arrhythmias is not known since several minutes most often elapse between collapse and rhythm assessment. Most patients with previous termout-of-hospital cardiac arrestnext term have a previous termcardiacnext term aetiology. previous termOut-of-hospital cardiac arrestsnext term most frequently occur in the patient's home, but the prognosis is shown to be better when they occur in a public place. Witnessed previous termarrest,next term ventricular fibrillation as initial arrhythmia and cardiopulmonary resuscitation are important predictors for immediate survival. In the long-term perspective, previous termcardiac arrestnext term in connection with acute myocardial infarction, high left ventricular ejection fraction, moderate age, absence of other heart failure signs and no history of myocardial infarction promotes better prognosis. Still there is much to learn about time trends, the influence of patient characteristics, comorbidity and previous termhospitalnext term treatment among patients with prehospital previous termcardiac arrest.
|
|
| 17. |
- Freedman, Ben, et al.
(författare)
-
Screening for Atrial Fibrillation A Report of the AF-SCREEN International Collaboration
- 2017
-
Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 135:19, s. 1851-
-
Tidskriftsartikel (refereegranskat)abstract
- Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country-and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.
|
|
| 18. |
- Klementieva, O., et al.
(författare)
-
Nano-scale Infrared Imaging of β-sheet Structures in Synaptic Junctions of Primary Neurons Isolated from Transgenic Mice
- 2018
-
Ingår i: 2018 43rd International Conference on Infrared Millimeter and Terahertz Waves, IRMMW-THz 2018. - 9781538638095 ; 2018-September
-
Konferensbidrag (refereegranskat)abstract
- Aβ is a class of aggregation-prone proteins, which may misfold into stable, β-sheet rich fibrils. Aβ is linked to the development of synaptic pathology in Alzheimer's disease (AD). However, a main question in the AD field is how Aβ contributes to AD neuropathology? Up to now there is little evidence for protein structural changes in diseased neuron. Our aim is to study the distribution of β-sheet structures in AD transgenic neurons in order to uncover sub-cellular mechanism(s) by which amyloid β-sheet structures are involved in AD pathology.
|
|
| 19. |
- Larsen, R. Wugt, et al.
(författare)
-
High-resolution infrared study of collisionally cooled trans-1,2-dichloroethylene
- 2007
-
Ingår i: Journal of Molecular Spectroscopy. - : Elsevier BV. - 0022-2852. ; 243:1, s. 99-102
-
Tidskriftsartikel (refereegranskat)abstract
- A recently constructed long-path enclosive flow cooling apparatus is employed to obtain the Fourier transform gas-phase infrared absorption spectrum of natural isotopic trans-1,2-dichloroethylene with a resolution of 0.00190 cm(-1) in the 800-1000 cm(-1) spectral region. The rotational structure of the out-of-plane CH flapping fundamental has been analyzed for the isotopic analogues Cl-35(2) and (ClCl)-Cl-35-Cl-37 using the Watson A-reduced Hamiltonian model and I-r-representation. A ground-state combination difference analysis for the (ClCl)-Cl-35-Cl-37 isotopomer based on 1402 assigned transitions belonging to the v(6) band yields a band origin of 897.94493(10) cm(-1) and values for the ground-state rotational constants: A(0) = 1.7466454(44) cm(-1), B-0 = 0.05019643(82) cm(-1) and C-0 = 0.04877977(82) cm(-1) together with quartic centrifugal distortion constants. The red-shift of 0.00444(10) cm(-1) observed for the v(6) band origin of (ClCl)-Cl-35-Cl-37 relative to the Cl-35(2), band origin is now consistent with the Rayleigh rule. (c) 2007 Elsevier Inc. All rights reserved.
|
|
| 20. |
- Lindgren, Johan, et al.
(författare)
-
Soft-tissue evidence for homeothermy and crypsis in a Jurassic ichthyosaur
- 2018
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 564:7736
-
Tidskriftsartikel (refereegranskat)abstract
- Ichthyosaurs are extinct marine reptiles that display a notable external similarity to modern toothed whales. Here we show that this resemblance is more than skin deep. We apply a multidisciplinary experimental approach to characterize the cellular and molecular composition of integumental tissues in an exceptionally preserved specimen of the Early Jurassic ichthyosaur Stenopterygius. Our analyses recovered still-flexible remnants of the original scaleless skin, which comprises morphologically distinct epidermal and dermal layers. These are underlain by insulating blubber that would have augmented streamlining, buoyancy and homeothermy. Additionally, we identify endogenous proteinaceous and lipid constituents, together with keratinocytes and branched melanophores that contain eumelanin pigment. Distributional variation of melanophores across the body suggests countershading, possibly enhanced by physiological adjustments of colour to enable photoprotection, concealment and/or thermoregulation. Convergence of ichthyosaurs with extant marine amniotes thus extends to the ultrastructural and molecular levels, reflecting the omnipresent constraints of their shared adaptation to pelagic life.
|
|
| 21. |
- Magnusson, Jesper, et al.
(författare)
-
Separation of the energy absorption and overvoltage protection in solid-state breakers by the use of parallel varistors
- 2014
-
Ingår i: IEEE transactions on power electronics. - 0885-8993 .- 1941-0107. ; 29:6, s. 2715-2722
-
Tidskriftsartikel (refereegranskat)abstract
- Hybrid and solid-state breakers offer new possibilities in the power grid by enabling faster switching, and by simplifying dc breaking. However, they consists of expensive power electronic components that are sensitive to overvoltage transients and require energy absorbing elements mounted in parallel. At turn-off, the rapidly decreasing current in the power electronic switch and the presence of an inherent stray inductance leads to hazardous overvoltage transients across the breaker. This paper investigates the possibility to split the overvoltage protection and energy absorption into two separate components. By optimizing the voltage ratio between two varistors, one can dimension a small electronics varistor for overvoltage protection and a large power electronics varistor for energy absorption. With this setup the power electronics varistor is allowed to be in a circuit with a large stray inductance and can thus be placed further away without causing an uncontrolled overvoltage. It is shown both in circuit simulations as well as in a small-scale experiment that if the voltage ratio between the two varistors is large enough, the inner varistor only has to absorb 1-2% of the system energy.
|
|
| 22. |
- Trokovic, N., et al.
(författare)
-
Exosomal secretion of death bullets: a new way of apoptotic escape?
- 2012
-
Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 303:8
-
Tidskriftsartikel (refereegranskat)abstract
- Trokovic N, Pollanen R, Porola P, Stegaev V, Hetzel U, Tivesten A, Engdahl C, Carlsten H, Forsblad-D'Elia H, Fagman JB, Lagerquist M, Konttinen YT. Exosomal secretion of death bullets: a new way of apoptotic escape? Am J Physiol Endocrinol Metab 303: E1015-E1024, 2012. First published August 12, 2012; doi: 10.1152/ajpendo.00139.2012.-Ovariectomy/estrogen deficiency causes selective apoptosis of the serous epithelial cells of the submandibular glands (SMG) in female mice. Because such apoptosis does not occur in healthy, estrogen-deficient male mice, it was hypothesized that dihydrotestosterone (DHT) protects epithelial SMG cells against apoptosis. The antiapoptotic effect of DHT on human epithelial HSG cells exposed to tumor necrosis factor-alpha and cycloheximide was studied. Correspondingly, the proapoptotic effect of androgen deficiency was studied in orchiectomized (ORX) androgen-knockout (ARKO) and wild-type (WT) mice. The health state of the SMG cells was studied with Alcian blue-periodic acid Schiff (AB-PAS) and amylase staining and transmission electron microscopy (TEM). The eventual protective antiapoptotic effect of dehydroepiandrosterone (DHEA) treatment was tested in this model. Apoptosis was assessed using immunohistochemisty of cleaved effector caspase-3 and its activator caspase-8 and the TUNEL assay. To test for the bioavailability, intracrine metabolism and sex steroid effects of DHEA, cystein-rich secretory protein-3 (CRISP-3), and leucine-isoleucine-valine transport system 1 (LIV-1) were used as androgen-and estrogen-regulated biomarkers, respectively. DHT protected HSG cells against induced apoptosis. In mice, androgen deficiency resulted in extensive activation of apoptotic caspase-8/3 cascade in serous epithelial cells. However, in salivary glands, active caspases were not translocated to nuclei but secreted to salivary ducts in exosome-like particles, which are associated with weak AB-PAS and amylase staining of the androgen-deprived cells and reduced number of intracellular secretory granules. DHEA treatment suppressed induction of proapoptotic caspases and almost normalized mucins and amylase and ultramophology of the serous epithelial cells in WT ORX but not ARKO ORX mice. According to the CRISP-3 and LIV-1 markers, DHEA probably exerted its effects via intracrine conversion to DHT.
|
|
